Pathophysiology of Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity a...

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Veröffentlicht in:	International journal of molecular sciences Jg. 21; H. 17; S. 6275
Hauptverfasser:	Galicia-Garcia, Unai, Benito-Vicente, Asier, Jebari, Shifa, Larrea-Sebal, Asier, Siddiqi, Haziq, Uribe, Kepa B., Ostolaza, Helena, Martín, César
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland MDPI AG 30.08.2020 MDPI
Schlagworte:	Animals Blood Glucose - metabolism Cardiovascular disease Diabetes Diabetes Mellitus, Type 2 - physiopathology Epidemiology Ethnicity Family medical history Genomes Glucose Homeostasis Humans Hyperglycemia Inflammation Insulin resistance Insulin Secretion Lifestyles Metabolism Mortality Musculoskeletal system Obesity Pathogenesis Pathophysiology Physiology Population Review Risk factors cardiovascular disease liver adipocyte muscle pathophysiology type 2 diabetes mellitus β-cell insulin resistance
ISSN:	1422-0067, 1661-6596, 1422-0067
Online-Zugang:	Volltext
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Abstract	Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.
AbstractList	Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM. Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.
Author	Jebari, Shifa Uribe, Kepa B. Galicia-Garcia, Unai Benito-Vicente, Asier Siddiqi, Haziq Ostolaza, Helena Larrea-Sebal, Asier Martín, César
AuthorAffiliation	5 Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014 Donostia San Sebastián, Spain; kbelloso@cicbiomagune.es 2 Biofisika Institute (UPV/EHU, CSIC), Barrio Sarriena s/n., 48940 Leioa (Bizkaia), Spain; asier.benito@ehu.eus (A.B.-V.); sjebari001@ikasle.ehu.eus (S.J.); ofbmaplc@ehu.es (H.O.) 1 Fundación Biofisika Bizkaia, Barrio Sarriena s/n., 48940 Leioa (Bizkaia), Spain; u.galiciag@gmail.com (U.G.-G.); asierlarrea@yahoo.es (A.L.-S.) 3 Department of Biochemistry and Molecular Biology, Universidad del País Vasco UPV/EHU, Apdo. 644, 48080 Bilbao, Spain 4 Havard Medical School, 25 Shattuck St, Boston, MA 02115, USA; siddiqi.haziq1@gmail.com
AuthorAffiliation_xml	– name: 5 Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014 Donostia San Sebastián, Spain; kbelloso@cicbiomagune.es – name: 1 Fundación Biofisika Bizkaia, Barrio Sarriena s/n., 48940 Leioa (Bizkaia), Spain; u.galiciag@gmail.com (U.G.-G.); asierlarrea@yahoo.es (A.L.-S.) – name: 2 Biofisika Institute (UPV/EHU, CSIC), Barrio Sarriena s/n., 48940 Leioa (Bizkaia), Spain; asier.benito@ehu.eus (A.B.-V.); sjebari001@ikasle.ehu.eus (S.J.); ofbmaplc@ehu.es (H.O.) – name: 3 Department of Biochemistry and Molecular Biology, Universidad del País Vasco UPV/EHU, Apdo. 644, 48080 Bilbao, Spain – name: 4 Havard Medical School, 25 Shattuck St, Boston, MA 02115, USA; siddiqi.haziq1@gmail.com
Author_xml	– sequence: 1 givenname: Unai surname: Galicia-Garcia fullname: Galicia-Garcia, Unai – sequence: 2 givenname: Asier surname: Benito-Vicente fullname: Benito-Vicente, Asier – sequence: 3 givenname: Shifa surname: Jebari fullname: Jebari, Shifa – sequence: 4 givenname: Asier surname: Larrea-Sebal fullname: Larrea-Sebal, Asier – sequence: 5 givenname: Haziq surname: Siddiqi fullname: Siddiqi, Haziq – sequence: 6 givenname: Kepa B. surname: Uribe fullname: Uribe, Kepa B. – sequence: 7 givenname: Helena surname: Ostolaza fullname: Ostolaza, Helena – sequence: 8 givenname: César orcidid: 0000-0002-4087-8729 surname: Martín fullname: Martín, César
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32872570$$D View this record in MEDLINE/PubMed
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Keywords	cardiovascular disease liver adipocyte muscle pathophysiology type 2 diabetes mellitus β-cell insulin resistance
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Snippet	Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by...
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SubjectTerms	Animals Blood Glucose - metabolism Cardiovascular disease Diabetes Diabetes Mellitus, Type 2 - physiopathology Epidemiology Ethnicity Family medical history Genomes Glucose Homeostasis Humans Hyperglycemia Inflammation Insulin resistance Insulin Secretion Lifestyles Metabolism Mortality Musculoskeletal system Obesity Pathogenesis Pathophysiology Physiology Population Review Risk factors
Title	Pathophysiology of Type 2 Diabetes Mellitus
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