PTEN Mutations as a Cause of Constitutive Insulin Sensitivity and Obesity
Evidence suggests that protection against cancer confers a risk of type 2 diabetes and vice versa. This study shows that persons susceptible to cancer owing to a constitutive mutation in the tumor-suppressor gene PTEN also have heightened sensitivity to insulin and are obese. Epidemiologic evidence...
Gespeichert in:
| Veröffentlicht in: | The New England journal of medicine Jg. 367; H. 11; S. 1002 - 1011 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
Waltham, MA
Massachusetts Medical Society
13.09.2012
|
| Schlagworte: | |
| ISSN: | 0028-4793, 1533-4406, 1533-4406 |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Evidence suggests that protection against cancer confers a risk of type 2 diabetes and vice versa. This study shows that persons susceptible to cancer owing to a constitutive mutation in the tumor-suppressor gene PTEN also have heightened sensitivity to insulin and are obese.
Epidemiologic evidence for a link among type 2 diabetes, obesity, and cancer has increased interest in the idea that some antidiabetes therapies may increase the risk of susceptibility to cancer, whereas others appear to offer protection.
1
Such a link is also supported by the discovery of several susceptibility loci for type 2 diabetes and their unexpected proximity to genes implicated in cell-cycle regulation.
2
The discovery of common genetic variants that influence both the risk of cancer and the risk of type 2 diabetes, in opposite directions, suggests that the two conditions may result from defects in the same pathway.
3
– . . . |
|---|---|
| AbstractList | Evidence suggests that protection against cancer confers a risk of type 2 diabetes and vice versa. This study shows that persons susceptible to cancer owing to a constitutive mutation in the tumor-suppressor gene PTEN also have heightened sensitivity to insulin and are obese.
Epidemiologic evidence for a link among type 2 diabetes, obesity, and cancer has increased interest in the idea that some antidiabetes therapies may increase the risk of susceptibility to cancer, whereas others appear to offer protection.
1
Such a link is also supported by the discovery of several susceptibility loci for type 2 diabetes and their unexpected proximity to genes implicated in cell-cycle regulation.
2
The discovery of common genetic variants that influence both the risk of cancer and the risk of type 2 diabetes, in opposite directions, suggests that the two conditions may result from defects in the same pathway.
3
– . . . Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTEN haploinsufficiency in humans.BACKGROUNDEpidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTEN haploinsufficiency in humans.We measured insulin sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness.METHODSWe measured insulin sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness.Measures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 32 [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution.RESULTSMeasures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 32 [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution.PTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.).CONCLUSIONSPTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.). BackgroundEpidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTEN haploinsufficiency in humans.MethodsWe measured insulin sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness.ResultsMeasures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 32 [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution.ConclusionsPTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.) Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTEN haploinsufficiency in humans. We measured insulin sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness. Measures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 32 [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution. PTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.). |
| Author | Karpe, Fredrik Walker, Lisa Van de Bunt, Martijn Linden, Helen Lachlan, Katherine L Levy, Jonathan C Gloyn, Anna L Barber, Thomas M Pal, Aparna Cooper, Nicola S Zhang, Qifeng Rudge, Simon A Wakelam, Michael J.O |
| Author_xml | – sequence: 1 givenname: Aparna surname: Pal fullname: Pal, Aparna organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 2 givenname: Thomas M surname: Barber fullname: Barber, Thomas M organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 3 givenname: Martijn surname: Van de Bunt fullname: Van de Bunt, Martijn organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 4 givenname: Simon A surname: Rudge fullname: Rudge, Simon A organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 5 givenname: Qifeng surname: Zhang fullname: Zhang, Qifeng organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 6 givenname: Katherine L surname: Lachlan fullname: Lachlan, Katherine L organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 7 givenname: Nicola S surname: Cooper fullname: Cooper, Nicola S organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 8 givenname: Helen surname: Linden fullname: Linden, Helen organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 9 givenname: Jonathan C surname: Levy fullname: Levy, Jonathan C organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 10 givenname: Michael J.O surname: Wakelam fullname: Wakelam, Michael J.O organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 11 givenname: Lisa surname: Walker fullname: Walker, Lisa organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 12 givenname: Fredrik surname: Karpe fullname: Karpe, Fredrik organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom – sequence: 13 givenname: Anna L surname: Gloyn fullname: Gloyn, Anna L organization: From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham (N.S.C.) — all in the United Kingdom |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26324996$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22970944$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kV1LHDEUhkOx1FV72dsSkII30-ZrMpMboSyrbvELaq_DmUymzTKT6CQj7L83umtbBUMg5OQ573lPzh7a8cFbhD5R8pWSUn67XPy4CEAp5UrKd2hGS84LIYjcQTNCWF2ISvFdtBfjiuRFhfqAdhlTFVFCzNDy-mZxiS-mBMkFHzHkjecwRYtDh-c5lFyakru3eOnj1DuPf1ofXY64tMbgW3zV2HxfH6D3HfTRftye--jXyeJmflacX50u59_PC1MKmgrDWkoVYzVQ1cimYxZUW3dl08pOASkNl6TilvC2yWHSKFo1StJaMOi4aBXfR8cb3dupGWxrrE8j9Pp2dAOMax3A6Zcv3v3Rv8O9FqRiJRFZ4GgrMIa7ycakBxeN7XvwNkxRU8JVXfOKyYwevkJXYRp9bu-JEqzKaKY-_-_or5XnX87Aly0A0UDfjeCNi_84yZlQ6rEc33BmDDGOttPGbQaTG3F9rqkfZ65fzDxnFa-ynoXf4rduhiFqb1fDG9wDj7y3vg |
| CODEN | NEJMAG |
| CitedBy_id | crossref_primary_10_1016_j_jbc_2025_108556 crossref_primary_10_1038_s41598_025_05233_4 crossref_primary_10_1080_16546628_2017_1412794 crossref_primary_10_3390_biom12020208 crossref_primary_10_1016_j_mce_2014_06_005 crossref_primary_10_3389_fonc_2015_00024 crossref_primary_10_1080_00325481_2019_1657358 crossref_primary_10_1111_jre_13141 crossref_primary_10_3389_fgene_2019_01133 crossref_primary_10_1007_s00125_017_4270_y crossref_primary_10_1016_j_lfs_2020_118145 crossref_primary_10_1007_s10557_014_6546_5 crossref_primary_10_1016_j_ghir_2015_01_003 crossref_primary_10_1111_cge_12055 crossref_primary_10_1038_s41416_020_0910_y crossref_primary_10_1111_jcmm_15232 crossref_primary_10_1038_s42255_020_00311_5 crossref_primary_10_1111_tra_12175 crossref_primary_10_1016_j_ygcen_2014_06_029 crossref_primary_10_1016_j_bbrc_2014_07_010 crossref_primary_10_3390_ijms26062770 crossref_primary_10_1038_nrc3397 crossref_primary_10_3892_ijmm_2017_2988 crossref_primary_10_3390_ijms24098441 crossref_primary_10_1093_hmg_ddt347 crossref_primary_10_1038_s41392_022_01149_x crossref_primary_10_7554_eLife_90419_2 crossref_primary_10_1056_NEJMra1100265 crossref_primary_10_1111_jne_12685 crossref_primary_10_1038_nature_2014_15665 crossref_primary_10_1186_s13023_021_02079_7 crossref_primary_10_1002_ajmg_a_63195 crossref_primary_10_1136_bcr_2013_201908 crossref_primary_10_3390_genes11070719 crossref_primary_10_1016_j_jbc_2021_100968 crossref_primary_10_3390_ijms21228691 crossref_primary_10_1016_j_cell_2013_03_002 crossref_primary_10_1002_pdi_1919 crossref_primary_10_1016_j_cell_2021_12_016 crossref_primary_10_1016_j_ymeth_2014_12_009 crossref_primary_10_1016_j_biopha_2023_114244 crossref_primary_10_1186_s12864_016_2538_0 crossref_primary_10_1194_jlr_O072629 crossref_primary_10_1002_mgg3_632 crossref_primary_10_1016_j_ydbio_2017_03_023 crossref_primary_10_3390_cancers11060844 crossref_primary_10_1186_s13046_018_0898_9 crossref_primary_10_1016_j_lfs_2020_117546 crossref_primary_10_1038_nrendo_2012_186 crossref_primary_10_20945_2359_3997000000007 crossref_primary_10_1002_oby_20852 crossref_primary_10_1097_MED_0000000000000426 crossref_primary_10_3390_genes12030358 crossref_primary_10_1161_HYPERTENSIONAHA_113_02526 crossref_primary_10_1111_joim_13090 crossref_primary_10_1002_mgg3_1130 crossref_primary_10_1007_s00592_020_01582_w crossref_primary_10_3390_ijms222011137 crossref_primary_10_1038_nrg_2016_56 crossref_primary_10_1038_s41387_018_0045_x crossref_primary_10_1016_j_clnu_2017_10_021 crossref_primary_10_1093_cvr_cvy077 crossref_primary_10_1371_journal_pone_0166956 crossref_primary_10_1038_s41418_019_0344_3 crossref_primary_10_3389_fnut_2020_00081 crossref_primary_10_1038_mp_2016_84 crossref_primary_10_1016_j_tem_2012_11_002 crossref_primary_10_1016_j_bbrc_2015_04_063 crossref_primary_10_1016_j_gastha_2023_10_012 crossref_primary_10_1038_srep16262 crossref_primary_10_1038_srep30265 crossref_primary_10_1186_s12986_021_00552_5 crossref_primary_10_1016_j_cmet_2015_02_017 crossref_primary_10_1186_s13098_019_0494_y crossref_primary_10_1038_s41598_017_17809_w crossref_primary_10_1186_s40348_022_00135_1 crossref_primary_10_1111_dom_12400 crossref_primary_10_18632_aging_100704 crossref_primary_10_1007_s11892_013_0429_1 crossref_primary_10_7554_eLife_90419 crossref_primary_10_1007_s00125_020_05228_y crossref_primary_10_1016_j_tins_2024_06_006 crossref_primary_10_1056_NEJMe1208934 crossref_primary_10_1038_s10038_020_0753_7 crossref_primary_10_1016_j_ymeth_2014_10_011 crossref_primary_10_1186_s12943_018_0803_3 crossref_primary_10_1530_ERC_17_0442 crossref_primary_10_1097_MD_0000000000031489 crossref_primary_10_1007_s13340_020_00455_5 crossref_primary_10_1016_j_ejmg_2015_08_005 crossref_primary_10_1016_j_gene_2025_149748 crossref_primary_10_1093_jmcb_mjv020 crossref_primary_10_1002_ajmg_c_31743 crossref_primary_10_1016_j_ygcen_2017_01_018 crossref_primary_10_1111_liv_12600 crossref_primary_10_1111_liv_15830 crossref_primary_10_2217_dmt_13_49 crossref_primary_10_1038_s41366_019_0367_3 crossref_primary_10_3390_ijms19113608 crossref_primary_10_1007_s11695_021_05231_1 crossref_primary_10_1016_j_cmet_2014_07_008 crossref_primary_10_3389_fphys_2018_00883 crossref_primary_10_1016_j_ajhg_2017_08_016 crossref_primary_10_1186_s40364_015_0047_y crossref_primary_10_1016_j_jbior_2014_07_002 crossref_primary_10_1038_celldisc_2016_54 crossref_primary_10_1038_ijo_2015_95 crossref_primary_10_1186_s12933_016_0443_0 crossref_primary_10_1200_JCO_2014_60_3456 crossref_primary_10_1158_1078_0432_CCR_13_2010 crossref_primary_10_1371_journal_pone_0061756 crossref_primary_10_3390_nu14071516 crossref_primary_10_1210_er_2018_00107 crossref_primary_10_3390_medicina60050767 crossref_primary_10_1056_NEJMc1212931 crossref_primary_10_1016_j_ajhg_2013_05_023 crossref_primary_10_1093_brain_awu031 crossref_primary_10_3389_fphys_2015_00004 crossref_primary_10_1002_pdi_2109 crossref_primary_10_3389_fendo_2021_628907 crossref_primary_10_1172_JCI84708 crossref_primary_10_1093_cvr_cvv016 crossref_primary_10_1038_nrm_2017_89 crossref_primary_10_1111_cge_12262 crossref_primary_10_3390_cancers16234010 crossref_primary_10_1038_srep09154 crossref_primary_10_3390_cells13151298 crossref_primary_10_1016_j_dsx_2013_08_001 crossref_primary_10_1016_j_numecd_2013_05_001 crossref_primary_10_1016_j_bbadis_2013_05_022 crossref_primary_10_1186_s42234_025_00172_x crossref_primary_10_1016_j_ygcen_2017_08_023 crossref_primary_10_1080_17446651_2016_1191349 crossref_primary_10_1016_j_bbrc_2019_04_033 crossref_primary_10_3389_fped_2025_1499664 crossref_primary_10_1210_er_2012_1041 crossref_primary_10_1172_JCI73579 crossref_primary_10_1007_s11892_019_1142_5 crossref_primary_10_1007_s13311_015_0356_8 crossref_primary_10_1093_ije_dyx132 crossref_primary_10_1146_annurev_med_052218_125823 crossref_primary_10_1016_j_immuni_2013_02_021 crossref_primary_10_3390_ijms160612051 crossref_primary_10_1007_s00109_015_1322_y crossref_primary_10_3389_fendo_2023_1226655 crossref_primary_10_3390_jcm10225457 crossref_primary_10_1016_j_ando_2017_01_001 crossref_primary_10_3892_etm_2021_10269 crossref_primary_10_1002_ijc_30840 crossref_primary_10_1016_j_bbamcr_2015_09_020 crossref_primary_10_7717_peerj_13867 crossref_primary_10_1016_j_bbadis_2014_09_002 crossref_primary_10_1111_cas_13116 crossref_primary_10_1002_path_6009 crossref_primary_10_1093_hmg_ddw154 crossref_primary_10_1038_nrclinonc_2016_120 crossref_primary_10_1016_j_ymeth_2015_02_009 crossref_primary_10_1016_j_bbadis_2013_05_011 crossref_primary_10_1080_10408363_2020_1746735 crossref_primary_10_1177_10668969251359942 crossref_primary_10_1038_nature14132 crossref_primary_10_3390_ijms252313169 crossref_primary_10_1016_j_tem_2023_10_009 crossref_primary_10_1007_s00395_013_0352_2 crossref_primary_10_1016_j_diabet_2016_03_003 crossref_primary_10_3389_fgene_2018_00353 crossref_primary_10_3389_fnmol_2021_756499 crossref_primary_10_1007_s13669_013_0074_3 |
| Cites_doi | 10.1093/hmg/ddg288 10.1128/MCB.00238-06 10.1038/ejhg.2008.162 10.1093/jnci/dji376 10.1038/nature10275 10.1038/ng.91 10.1007/s00125-006-0531-x 10.1042/BST20051045 10.1111/j.1464-5491.1994.tb00273.x 10.1038/nrm2043 10.1016/j.cell.2012.02.030 10.2337/diacare.21.12.2191 10.1073/pnas.0308617100 10.1128/MCB.25.3.1135-1145.2005 10.1016/S0140-6736(05)67402-8 10.1007/s00125-010-1815-8 10.1016/j.beem.2008.07.007 10.1038/ng2062 10.1517/13543784.15.8.917 10.1128/MCB.25.6.2498-2510.2005 10.1210/jc.2006-0166 10.1152/ajpendo.00586.2009 10.2337/diacare.23.3.295 10.2337/diacare.22.9.1462 10.1128/MCB.26.7.2772-2781.2006 10.1002/ajmg.1320410128 10.1002/pros.20732 10.1074/jbc.273.22.13375 10.1038/ng.520 |
| ContentType | Journal Article |
| Copyright | Copyright © 2012 Massachusetts Medical Society. All rights reserved. 2015 INIST-CNRS Copyright © 2012 Massachusetts Medical Society. 2012 |
| Copyright_xml | – notice: Copyright © 2012 Massachusetts Medical Society. All rights reserved. – notice: 2015 INIST-CNRS – notice: Copyright © 2012 Massachusetts Medical Society. 2012 |
| DBID | AAYXX CITATION IQODW CGR CUY CVF ECM EIF NPM 7RV 7X7 7XB 8AO 8C1 8FE 8FH 8FI ABUWG AFKRA AN0 AZQEC BBNVY BEC BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ GUQSH HCIFZ K0Y LK8 M0R M0T M1P M2M M2O M2P M7P MBDVC NAPCQ PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS PSYQQ Q9U 7X8 5PM |
| DOI | 10.1056/NEJMoa1113966 |
| DatabaseName | CrossRef Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Nursing & Allied Health Database Health & Medical Collection ProQuest Central (purchase pre-March 2016) ProQuest Pharma Collection Public Health Database ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection ProQuest Central (Alumni) ProQuest Central UK/Ireland British Nursing Database ProQuest Central Essentials Biological Science Collection eLibrary AUTh Library subscriptions: ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student Research Library Prep SciTech Premium Collection New England Journal of Medicine ProQuest Biological Science Collection Consumer Health Database Healthcare Administration Database Medical Database ProQuest Psychology Database ProQuest research library Science Database Biological Science Database Research Library (Corporate) Nursing & Allied Health Premium ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China ProQuest One Psychology ProQuest Central Basic MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest One Psychology Research Library Prep ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials elibrary ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing New England Journal of Medicine ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Research Library ProQuest Central (New) ProQuest Public Health ProQuest Biological Science Collection ProQuest Central Basic ProQuest Science Journals ProQuest Family Health ProQuest One Academic Eastern Edition British Nursing Index with Full Text ProQuest Health Management ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest Medical Library ProQuest Psychology Journals ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic ProQuest One Psychology MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7RV name: Nursing & Allied Health Database url: https://search.proquest.com/nahs sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1533-4406 |
| EndPage | 1011 |
| ExternalDocumentID | PMC4072504 2760485971 22970944 26324996 10_1056_NEJMoa1113966 NJ201209133671107 |
| Genre | Original Article Research Support, Non-U.S. Gov't Journal Article |
| GeographicLocations | United Kingdom--UK |
| GeographicLocations_xml | – name: United Kingdom--UK |
| GrantInformation_xml | – fundername: Wellcome Trust grantid: 095101 – fundername: Biotechnology and Biological Sciences Research Council grantid: BBS/E/B/000C0415 – fundername: Medical Research Council grantid: G0800467 – fundername: Biotechnology and Biological Sciences Research Council grantid: BBS/E/B/0000C227 – fundername: Biotechnology and Biological Sciences Research Council grantid: BBS/E/B/000C0413 – fundername: Wellcome Trust grantid: 095101/Z/10Z – fundername: Medical Research Council grantid: G0700222 |
| GroupedDBID | - 0R 0WA 123 186 1KJ 1VV 29N 2KS 2WC 34G 39C 3O- 3V. 4 4.4 53G 55 5D0 5RE 68V 7FN 7RV 7X7 85S 8AO 8C1 8FE 8FH 8FI AACLI AAEJM AAIKC AALRV AAPBV AAQQT AARDX AAWTL ABACO ABEHJ ABFLS ABIVO ABOCM ABPPZ ABPTK ABQIJ ABUWG ABWJO ACGFS ACGOD ACJLH ACNCT ACPRK ACRZS ADBBV ADBIT ADCBC ADRHT AENEX AETEA AFDAS AFFNX AFHKK AFKRA AGFXO AGNAY AHMBA AJJEV AJVPN ALMA_UNASSIGNED_HOLDINGS AN0 AQUVI AZQEC BBAFP BBNVY BCR BCU BENPR BES BHPHI BKEYQ BKNYI BLC BNQBC BPHCQ BVXVI C45 CJ0 CO CS3 DCD DU5 DWQXO DZ EBS EJD ET EX3 F20 F5P FD8 FM. FYUFA G8K GJ GNUQQ GUQSH H13 HCIFZ HZ IH2 K-O K78 KM KOO L7B LK8 M0R M0T M1P M2M M2O M2P M7P MVM N9A NAPCQ NEJ O9- OK1 OMK OVD P-O P-S P2P PADUT PCD PEA PQEST PQQKQ PQUKI PRINS PROAC PSQYO QJJ RHI RWL RXW S10 S6N SJFOW SJN TAE TAF TEORI TN5 TUQ TWZ UCV UKR UMD UQL VQA W2G WH7 WOQ WOW X X7M XJT XYN XZL YCJ YNT YRY YZZ ZA5 ZHY ZKB --- -DZ -ET -~X .-4 .55 .CO .GJ 0R~ 1CY 36B 6TJ AAMNW AAYXX ABBLC ABCQX ABDPE ABDQB ABJNI ABUFD ACKOT ACPFK ADUKH ADXHL AERZD AFFHD AGHSJ BYPQX CCPQU CITATION HF~ HMCUK HZ~ N4W PHGZM PHGZT PJZUB PPXIY PQGLB PSYQQ UKHRP YFH YR2 YR5 YYP ZCA ZR0 ZVN ~KM 41~ 8WZ 9M8 A6W AAQOH AAUTI ABEFU ACPVT ACTDY AFFDN AFOSN AJUXI ALIPV D0S FA8 IQODW J5H LPU MQT NHB OHT QZG SKT UBX WHG XOL YHZ YQI YQJ YYQ ZGI ZXP CGR CUY CVF ECM EIF NPM 7XB BEC K0Y MBDVC PKEHL Q9U 7X8 5PM |
| ID | FETCH-LOGICAL-c541t-c2d119228a19b6bf2ea9d8f5bd6f9a05c36073e03dbd8f0b917b961842af34d93 |
| IEDL.DBID | DCD |
| ISICitedReferencesCount | 188 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000308649100006&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0028-4793 1533-4406 |
| IngestDate | Tue Nov 04 01:55:21 EST 2025 Sun Nov 09 13:29:58 EST 2025 Thu Oct 30 08:48:10 EDT 2025 Mon Nov 17 00:33:42 EST 2025 Mon Jul 21 09:15:44 EDT 2025 Tue Nov 18 21:32:31 EST 2025 Sat Nov 29 03:54:32 EST 2025 Tue Dec 21 14:38:54 EST 2021 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 11 |
| Keywords | Medicine Obesity Pancreatic hormone Nutrition disorder Cause Genetics PTEN Gene Mutation Insulin Nutritional status Tumor suppressor gene |
| Language | English |
| License | CC BY 4.0 |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c541t-c2d119228a19b6bf2ea9d8f5bd6f9a05c36073e03dbd8f0b917b961842af34d93 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| OpenAccessLink | http://doi.org/10.1056/NEJMoa1113966 |
| PMID | 22970944 |
| PQID | 1039427398 |
| PQPubID | 40644 |
| PageCount | 10 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_4072504 proquest_miscellaneous_1039883726 proquest_journals_1039427398 pubmed_primary_22970944 pascalfrancis_primary_26324996 crossref_citationtrail_10_1056_NEJMoa1113966 crossref_primary_10_1056_NEJMoa1113966 mms_nejm_10_1056_NEJMoa1113966 |
| PublicationCentury | 2000 |
| PublicationDate | 2012-09-13 |
| PublicationDateYYYYMMDD | 2012-09-13 |
| PublicationDate_xml | – month: 09 year: 2012 text: 2012-09-13 day: 13 |
| PublicationDecade | 2010 |
| PublicationPlace | Waltham, MA |
| PublicationPlace_xml | – name: Waltham, MA – name: United States – name: Boston |
| PublicationTitle | The New England journal of medicine |
| PublicationTitleAlternate | N Engl J Med |
| PublicationYear | 2012 |
| Publisher | Massachusetts Medical Society |
| Publisher_xml | – name: Massachusetts Medical Society |
| References | Kloting, N, Fasshauer, M, Dietrich, A (r028) 2010; 299 Nguyen, KT, Tajmir, P, Lin, CH (r013) 2006; 26 Semple, RK, Soos, MA, Luan, J (r029) 2006; 91 Maehama, T, Dixon, JE (r008) 1998; 273 Thomas, G, Jacobs, KB, Yeager, M (r005) 2008; 40 Iida, S, Ono, A, Sayama, K (r025) 2000; 20 Wei, EK, Giovannucci, E, Fuchs, CS, Willett, WC, Mantzoros, CS (r030) 2005; 97 Holly, JM, Perks, CM (r006) 2008; 22 Goberdhan, DC, Wilson, C (r007) 2003; 12 Kurlawalla-Martinez, C, Stiles, B, Wang, Y, Devaskar, SU, Kahn, BB, Wu, H (r012) 2005; 25 Wijesekara, N, Konrad, D, Eweida, M (r016) 2005; 25 Levy, JC, Matthews, DR, Hermans, MP (r020) 1998; 21 Cole, TR, Hughes, HE (r024) 1991; 41 Dupuis, J, Langenberg, C, Prokopenko, I (r002) 2010; 42 Alberti, KG, Zimmet, P, Shaw, J (r023) 2005; 366 DeFronzo, RA, Tobin, JD, Andres, R (r022) 1979; 237 Stiles, BL, Kuralwalla-Martinez, C, Guo, W (r015) 2006; 26 Berger, AH, Knudson, AG, Pandolfi, PP (r017) 2011; 476 Wong, JT, Kim, PT, Peacock, JW (r011) 2007; 50 Cohen, P (r010) 2006; 7 Stumvoll, M, Mitrakou, A, Pimenta, W (r019) 2000; 23 Phillips, DI, Clark, PM, Hales, CN, Osmond, C (r021) 1994; 11 Matsuda, M, DeFronzo, RA (r018) 1999; 22 Garcia-Cao, I, Song, MS, Hobbs, RM (r027) 2012; 149 Karpe, F, Tan, GD (r026) 2005; 33 Blumenthal, GM, Dennis, PA (r009) 2008; 16 Agalliu, I, Suuriniemi, M, Prokunina-Olsson, L (r004) 2008; 68 Barb, D, Pazaitou-Panayiotou, K, Mantzoros, CS (r031) 2006; 15 Smith, U, Gale, EA (r001) 2010; 53 Gudmundsson, J, Sulem, P, Steinthorsdottir, V (r003) 2007; 39 Stiles, B, Wang, Y, Stahl, A (r014) 2004; 101 r020 r021 r001 r023 r017 r018 r019 r013 r014 r015 r016 DeFronzo RA (r022) 1979; 237 r031 r010 Iida S (r025) 2000; 20 r011 r012 r030 r006 r028 r007 r029 r008 r009 r002 r024 r003 r004 r026 r005 r027 23032179 - Nat Rev Endocrinol. 2012 Dec;8(12):698. doi: 10.1038/nrendo.2012.186. 23252536 - N Engl J Med. 2012 Dec 20;367(25):2450-1; author reply 2451. doi: 10.1056/NEJMc1212931. 22970949 - N Engl J Med. 2012 Sep 13;367(11):1061-3. doi: 10.1056/NEJMe1208934. |
| References_xml | – volume: 42 start-page: 105 year: 2010 end-page: 116 ident: r002 article-title: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. publication-title: Nat Genet ;[Erratum, Nat Genet 2010;42:464.] – volume: 25 start-page: 1135 year: 2005 end-page: 1145 ident: r016 article-title: Muscle-specific Pten deletion protects against insulin resistance and diabetes. publication-title: Mol Cell Biol – volume: 23 start-page: 295 year: 2000 end-page: 301 ident: r019 article-title: Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. publication-title: Diabetes Care – volume: 101 start-page: 2082 year: 2004 end-page: 2087 ident: r014 article-title: Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity. publication-title: Proc Natl Acad Sci U S A ;[Erratum, Proc Natl Acad Sci U S A 2004;101:5180.] – volume: 53 start-page: 1541 year: 2010 end-page: 1544 ident: r001 article-title: Cancer and diabetes: are we ready for prime time? publication-title: Diabetologia – volume: 41 start-page: 115 year: 1991 end-page: 124 ident: r024 article-title: Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome? publication-title: Am J Med Genet – volume: 273 start-page: 13375 year: 1998 end-page: 13378 ident: r008 article-title: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. publication-title: J Biol Chem – volume: 16 start-page: 1289 year: 2008 end-page: 1300 ident: r009 article-title: PTEN hamartoma tumor syndromes. publication-title: Eur J Hum Genet – volume: 21 start-page: 2191 year: 1998 end-page: 2192 ident: r020 article-title: Correct homeostasis model assessment (HOMA) evaluation uses the computer program. publication-title: Diabetes Care – volume: 22 start-page: 1462 year: 1999 end-page: 1470 ident: r018 article-title: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. publication-title: Diabetes Care – volume: 149 start-page: 49 year: 2012 end-page: 62 ident: r027 article-title: Systemic elevation of PTEN induces a tumor-suppressive metabolic state. publication-title: Cell – volume: 476 start-page: 163 year: 2011 end-page: 169 ident: r017 article-title: A continuum model for tumour suppression. publication-title: Nature – volume: 50 start-page: 395 year: 2007 end-page: 403 ident: r011 article-title: Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity. publication-title: Diabetologia – volume: 68 start-page: 740 year: 2008 end-page: 747 ident: r004 article-title: Evaluation of a variant in the transcription factor 7-like 2 (TCF7L2) gene and prostate cancer risk in a population-based study. publication-title: Prostate – volume: 366 start-page: 1059 year: 2005 end-page: 1062 ident: r023 article-title: The metabolic syndrome -- a new worldwide definition. publication-title: Lancet – volume: 26 start-page: 2772 year: 2006 end-page: 2781 ident: r015 article-title: Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes. publication-title: Mol Cell Biol – volume: 39 start-page: 977 year: 2007 end-page: 983 ident: r003 article-title: Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. publication-title: Nat Genet – volume: 11 start-page: 286 year: 1994 end-page: 292 ident: r021 article-title: Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. publication-title: Diabet Med – volume: 237 start-page: E214 year: 1979 end-page: E223 ident: r022 article-title: Glucose clamp technique: a method for quantifying insulin secretion and resistance. publication-title: Am J Physiol – volume: 91 start-page: 3219 year: 2006 end-page: 3223 ident: r029 article-title: Elevated plasma adiponectin in humans with genetically defective insulin receptors. publication-title: J Clin Endocrinol Metab – volume: 26 start-page: 4511 year: 2006 end-page: 4518 ident: r013 article-title: Essential role of Pten in body size determination and pancreatic beta-cell homeostasis in vivo. publication-title: Mol Cell Biol – volume: 15 start-page: 917 year: 2006 end-page: 931 ident: r031 article-title: Adiponectin: a link between obesity and cancer. publication-title: Expert Opin Investig Drugs – volume: 22 start-page: 539 year: 2008 end-page: 550 ident: r006 article-title: Cancer as an endocrine problem. publication-title: Best Pract Res Clin Endocrinol Metab – volume: 7 start-page: 867 year: 2006 end-page: 873 ident: r010 article-title: The twentieth century struggle to decipher insulin signalling. publication-title: Nat Rev Mol Cell Biol – volume: 33 start-page: 1045 year: 2005 end-page: 1048 ident: r026 article-title: Adipose tissue function in the insulin-resistance syndrome. publication-title: Biochem Soc Trans – volume: 299 start-page: E506 year: 2010 end-page: E515 ident: r028 article-title: Insulin-sensitive obesity. publication-title: Am J Physiol Endocrinol Metab – volume: 20 start-page: 1901 year: 2000 end-page: 1904 ident: r025 article-title: Accelerated decline of blood glucose after intravenous glucose injection in a patient with Cowden disease having a heterozygous germline mutation of the PTEN/MMAC1 gene. publication-title: Anticancer Res – volume: 97 start-page: 1688 year: 2005 end-page: 1694 ident: r030 article-title: Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. publication-title: J Natl Cancer Inst – volume: 40 start-page: 310 year: 2008 end-page: 315 ident: r005 article-title: Multiple loci identified in a genome-wide association study of prostate cancer. publication-title: Nat Genet – volume: 25 start-page: 2498 year: 2005 end-page: 2510 ident: r012 article-title: Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. publication-title: Mol Cell Biol – volume: 12 start-page: R239 year: 2003 end-page: R248 ident: r007 article-title: PTEN: tumour suppressor, multifunctional growth regulator and more. ;:Spec No 2 publication-title: Hum Mol Genet – volume: 20 start-page: 1901 year: 2000 ident: r025 publication-title: Anticancer Res – ident: r007 doi: 10.1093/hmg/ddg288 – ident: r013 doi: 10.1128/MCB.00238-06 – ident: r009 doi: 10.1038/ejhg.2008.162 – volume: 237 start-page: E214 year: 1979 ident: r022 publication-title: Am J Physiol – ident: r030 doi: 10.1093/jnci/dji376 – ident: r017 doi: 10.1038/nature10275 – ident: r005 doi: 10.1038/ng.91 – ident: r011 doi: 10.1007/s00125-006-0531-x – ident: r026 doi: 10.1042/BST20051045 – ident: r021 doi: 10.1111/j.1464-5491.1994.tb00273.x – ident: r010 doi: 10.1038/nrm2043 – ident: r027 doi: 10.1016/j.cell.2012.02.030 – ident: r020 doi: 10.2337/diacare.21.12.2191 – ident: r014 doi: 10.1073/pnas.0308617100 – ident: r016 doi: 10.1128/MCB.25.3.1135-1145.2005 – ident: r023 doi: 10.1016/S0140-6736(05)67402-8 – ident: r001 doi: 10.1007/s00125-010-1815-8 – ident: r006 doi: 10.1016/j.beem.2008.07.007 – ident: r003 doi: 10.1038/ng2062 – ident: r031 doi: 10.1517/13543784.15.8.917 – ident: r012 doi: 10.1128/MCB.25.6.2498-2510.2005 – ident: r029 doi: 10.1210/jc.2006-0166 – ident: r028 doi: 10.1152/ajpendo.00586.2009 – ident: r019 doi: 10.2337/diacare.23.3.295 – ident: r018 doi: 10.2337/diacare.22.9.1462 – ident: r015 doi: 10.1128/MCB.26.7.2772-2781.2006 – ident: r024 doi: 10.1002/ajmg.1320410128 – ident: r004 doi: 10.1002/pros.20732 – ident: r008 doi: 10.1074/jbc.273.22.13375 – ident: r002 doi: 10.1038/ng.520 – reference: 22970949 - N Engl J Med. 2012 Sep 13;367(11):1061-3. doi: 10.1056/NEJMe1208934. – reference: 23252536 - N Engl J Med. 2012 Dec 20;367(25):2450-1; author reply 2451. doi: 10.1056/NEJMc1212931. – reference: 23032179 - Nat Rev Endocrinol. 2012 Dec;8(12):698. doi: 10.1038/nrendo.2012.186. |
| SSID | ssj0000149 |
| Score | 2.5017087 |
| Snippet | Evidence suggests that protection against cancer confers a risk of type 2 diabetes and vice versa. This study shows that persons susceptible to cancer owing to... Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both... BackgroundEpidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles... |
| SourceID | pubmedcentral proquest pubmed pascalfrancis crossref mms |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 1002 |
| SubjectTerms | 1-Phosphatidylinositol 3-kinase Absorptiometry Adiponectin - blood Adipose Tissue Adult Aged AKT protein Anthropomorphism Beta cells Biological and medical sciences Biomedical research Biopsy Body composition Body mass Body Mass Index Cancer Cell growth Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Epidemiology Female General aspects Glucose Glucose Tolerance Test Haploinsufficiency Humans Insulin Insulin resistance Insulin Resistance - genetics Laboratories Leptin - blood Male Medical sciences Metabolic diseases Metabolism Middle Aged Mutation Neoplasms - complications Neoplasms - genetics Obesity Obesity - complications Obesity - genetics Phosphatase Phosphorylation Population studies PTEN Phosphohydrolase - genetics PTEN protein Skinfold thickness Tensin Thyroid gland |
| SummonAdditionalLinks | – databaseName: Biological Science Database dbid: M7P link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwEB7RghAX3o9AqYyEOBE1G9tJfEKoakUPXa1EkXqLxi_Rik1Ks8vvZ-x4d7uIckHKKR5Ziceeh2f0fQDva26dqrXOXe1dLirkOWqDubcoLRcFl76IZBP1dNqcn6tZunAbUlvlyiZGQ217E-7ID0LJUpCvVc2nq595YI0K1dVEobEDdwNKAo-te7Mb8FEp_E03SAljk3z-QWCa7zHwrKsIkLjxSTvz-RA6JHGgRfIju8Xfws8_uyhvuKXjR__7Q4_hYQpI2edxBz2BO657CvdPU8n9GZzMzo6m7HQ5luwHhvSwQ1wOjvWeBb7P2GxARpOdjH3t7Gtoih9ZKRh2liXygefw7fjo7PBLnvgXciPFZJGb0k4oACwbnChdaV86VLbxUtvKKyyk4RUZCFdwq-l1oSnz05FApkTPhVX8Bex2fedeAfO11IVzpioMCl5pRGxsaWuUgtbA6Aw-rjTQmgROHjgyfrSxSC6rdkthGXxYi1-NqBy3Ce6TOtvOXc5vFdjS9Hq6iGNPyWAGeyv1tel4D-1Gdxm8Ww_TwQzVFuxcvxxlGkr_S5ri5bhTNpOXqqa8WmRQb-2htUAA_d4e6S6-R_DvAGgnC_H635_1Bh5QZFeGxpYJ34PdxfXSvYV75tfiYrjej6fkN0RpGnA priority: 102 providerName: ProQuest |
| Title | PTEN Mutations as a Cause of Constitutive Insulin Sensitivity and Obesity |
| URI | https://nejm.org/doi/full/10.1056/NEJMoa1113966 https://www.ncbi.nlm.nih.gov/pubmed/22970944 https://www.proquest.com/docview/1039427398 https://www.proquest.com/docview/1039883726 https://pubmed.ncbi.nlm.nih.gov/PMC4072504 |
| Volume | 367 |
| WOSCitedRecordID | wos000308649100006&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVBGY databaseName: New England Journal of Medicine Current customDbUrl: eissn: 1533-4406 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: DCD dateStart: 19900101 isFulltext: true titleUrlDefault: https://www.nejm.org/medical-index providerName: Massachusetts Medical Society – providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M7P dateStart: 19800103 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Consumer Health Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M0R dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/familyhealth providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: 7X7 dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: Health Management Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M0T dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/healthmanagement providerName: ProQuest – providerCode: PRVPQU databaseName: Nursing & Allied Health Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: 7RV dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/nahs providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: BENPR dateStart: 19800103 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Psychology Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M2M dateStart: 19800103 isFulltext: true titleUrlDefault: https://www.proquest.com/psychology providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Research Library customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M2O dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/pqrl providerName: ProQuest – providerCode: PRVPQU databaseName: Public Health Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: 8C1 dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/publichealth providerName: ProQuest – providerCode: PRVPQU databaseName: Science Database customDbUrl: eissn: 1533-4406 dateEnd: 20250908 omitProxy: false ssIdentifier: ssj0000149 issn: 0028-4793 databaseCode: M2P dateStart: 19800103 isFulltext: true titleUrlDefault: https://search.proquest.com/sciencejournals providerName: ProQuest |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3db9MwED-tG0K88P0RGJWREE9ES-wkTh6h68QeWqpSUN-ic2xrQzRFS8vfz9lJywJMCCn6PcQXK_7Mne9yP4DXUmhTSKVCI60JkwxFiKrC0GpMtUgikdrIk03I6TRfLovZAZzs_oWpzdeVd-C7Fe1OoHfs8CeOG36NjhmdNPQBHNFcKxxXw-no9Fq-qE7f7Y6MuqSafzze-wgNVqvGhURiQ71iWzqLv-mbv4dNXvsOnd377xbch7udysnetXPkARyY-iHcnnRO9UdwPluMp2yybZ3yDUO62Ai3jWFryxyjpw8noG2RnbeR6-yTC3tveScY1pp19AKP4fPZeDH6EHYMC2GVJvEmrLiOScXjOcaFypTlBgud21TpzBYYpZXIaAswkdCKbkeKbDvlKWI4WpHoQjyBw3pdm2fArExVZEyVRRUmIlOImGuuJaZJwmWlAni76_Ky6tKPOxaMb6V3g6dZ2eueAN7sxb-3eTduEhzS-JWu128U6A3tvjqfqZ7MvQCOd2Nddgu4KZ2HnN5bFHkAr_bFtPScPwVrs962MjkZ-JyqeNpOjV-V80KS5ZwEIHuTZi_g0nr3S-rLC5_e26WsS6Pk-b8a9gLukPbGXfBKLI7hcHO1NS_hVvVjc9lcDWEg518cLqXHnDAfxUM4ej-ezuZDv3AIJ9Hc48Ihn3j86HHmUM5-AqwpFKY |
| linkProvider | Massachusetts Medical Society |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3LbtQwFL0qBQEb3o9AKUYCVkT12M5rgRAqrTpqZ1SJQeouvX6JIiYpzQyIn-IbsZ1kpoMouy6QskqurCQ-ub62T84BeJlxbYpMythk1sQiRR6jVBhbjYnmgvLE0mA2kY3H-dFRcbgGv_p_YTytss-JIVHrWvk18i2_ZSncWFvk706_xd41yu-u9hYaLSz2zc8fbsrWvB1-cP37irHdncn2Xty5CsQqEYNZrJgeuLKG5TgoZCotM1jo3CZSp7ZAmiieOtgbyrV0p6l08xkZbFEYWi60F19yKf-q19XzFMIRnZyTq-rK7W7FqtP0dDXGlne2r9H7uhdBkHE5Bl6ZThvPyMTGdYpt3TT-Vu7-ydo8Nwzu3v7fXuAduNUV3OR9-4XchTVT3YPro45ScB-Gh5OdMRnNW0pCQ9AdZBvnjSG1Jd7PNJAp3KBAhi1vn3z0pP_WdYNgpUlnrvAAPl3KgzyE9aquzGMgNkskNUalVKHgqUTEXDOdYSLcO1cygjd9j5eqE1_3HiBfy0ACSNJyBSARvF6En7aqIxcFbjr4lJX5Mr0wYAVZi-aCTr-b7Eaw0cOl7NJXUy6xEsGLxWWXePxuElamnrcxec4z5pp41CJz2TgrMloIEUG2gtlFgBc1X71SnXwO4uZesC-h4sm_b-s53NibjA7Kg-F4_yncdFUs8ySeAd-A9dnZ3DyDa-r77KQ52wxfKIHjy0b0byGOd5s |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFD4aA028cL8ExjAS8ETUxHbi5AEh1K2iGqsqMaS9BV_FpjUZSwvir_HrOM6lXRHjbQ9IeWqOrCb-fHwcf_4-gJeCGZsLpUIrnA15KlkolZahMzIxjEcscVFjNiEmk-zoKJ9uwK_-LIynVfY5sUnUptL-G_nAb1lynGvzbOA6WsR0d_Tu7FvoHaT8Tmtvp9FCZN_-_IHLt_rteBf7-hWlo73D4YewcxgIdcLjeaipibHEoZmMc5UqR63MTeYSZVKXyyjRLMUhYCNmFP4cKVzbqMYihUrHuPFCTJj-rwuGKPan1IfxBemqrvTuvl51-p5Ybwy8y30lvcd73ogzrubDa7NZ7dmZssYOcq2zxt9K3z8ZnBemxNHt__ll3oFbXSFO3rcj5y5s2PIebB10VIP7MJ4e7k3IwaKlKtRE4kWGclFbUjnifU4bkgVOFmTc8vnJJ38YoHXjILI0pDNdeACfr-RBHsJmWZX2MRAnEhVZq9NIS85SJaXMDDVCJhzfv1YBvOl7v9CdKLv3BjktGnJAkhZrYAng9TL8rFUjuSxwB6FUlPZkdmnAGsqWzTX6_bgIDmC7h07RpbW6WOEmgBfL25iQ_C6TLG21aGOyjAmKTTxqUbpqnOYiyjkPQKzhdxngxc7X75THXxvRcy_kl0T8yb__1nPYQiAXH8eT_adwE4tb6rk9MduGzfn5wj6DG_r7_Lg-32kGK4EvVw3o33bUgBk |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=PTEN+Mutations+as+a+Cause+of+Constitutive+Insulin+Sensitivity+and+Obesity&rft.jtitle=The+New+England+journal+of+medicine&rft.au=Pal%2C+Aparna&rft.au=Barber%2C+Thomas+M.&rft.au=Van+de+Bunt%2C+Martijn&rft.au=Rudge%2C+Simon+A.&rft.date=2012-09-13&rft.issn=0028-4793&rft.eissn=1533-4406&rft.volume=367&rft.issue=11&rft.spage=1002&rft.epage=1011&rft_id=info:doi/10.1056%2FNEJMoa1113966&rft_id=info%3Apmid%2F22970944&rft.externalDocID=PMC4072504 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0028-4793&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0028-4793&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0028-4793&client=summon |