The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a resul...

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Published in:Cells (Basel, Switzerland) Vol. 8; no. 10; p. 1207
Main Authors: Holly, Jeff M. P., Biernacka, Kalina, Perks, Claire M.
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 06.10.2019
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Abstract When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.
AbstractList When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.
When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.
Author Holly, Jeff M. P.
Perks, Claire M.
Biernacka, Kalina
AuthorAffiliation Department of Translational Health Science, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UK; mdxkz@bristol.ac.uk (K.B.); claire.m.perks@bristol.ac.uk (C.M.P.)
AuthorAffiliation_xml – name: Department of Translational Health Science, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UK; mdxkz@bristol.ac.uk (K.B.); claire.m.perks@bristol.ac.uk (C.M.P.)
Author_xml – sequence: 1
  givenname: Jeff M. P.
  surname: Holly
  fullname: Holly, Jeff M. P.
– sequence: 2
  givenname: Kalina
  surname: Biernacka
  fullname: Biernacka, Kalina
– sequence: 3
  givenname: Claire M.
  surname: Perks
  fullname: Perks, Claire M.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31590432$$D View this record in MEDLINE/PubMed
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Keywords cancer
metabolism
insulin
diabetes
obesity
IGF-II
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PublicationPlace_xml – name: Switzerland
– name: Basel
PublicationTitle Cells (Basel, Switzerland)
PublicationTitleAlternate Cells
PublicationYear 2019
Publisher MDPI AG
MDPI
Publisher_xml – name: MDPI AG
– name: MDPI
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Snippet When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin...
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SubjectTerms Alternative splicing
Amino acids
Antisense RNA
cancer
Chromosomes
Diabetes
Diabetes mellitus
Gene duplication
Gene loci
Hypoglycemia
igf-ii
Insulin
Insulin-like growth factor II
Insulin-like growth factors
Metabolic disorders
Metabolism
mRNA
Non-coding RNA
obesity
Peptides
Physiology
Review
Tumors
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Title The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer
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