The TRIB3 Q84R polymorphism, insulin resistance and related metabolic alterations

Research output: Contribution to journalArticle

Abstract

Insulin resistance is pathogenic for many prevalent disorders including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), polycystic ovary syndrome, non-alcoholic fatty liver disease, Alzheimer's and Parkinson's diseases and several cancers. Unravelling molecular abnormalities of insulin resistance may therefore pave the way for tackling such heavy weight on healthcare systems. This review will be focused on studies addressing the role of genetic variability of TRIB3, an inhibitor of insulin signalling at the AKT level on insulin resistance and several related abnormalities. Studies carried out in several cultured cells clearly report that the TRIB3 Q84R missense polymorphism, is a gain-of-function amino acid substitution, with the Arg84 variant being a stronger inhibitor of insulin-mediated AKT activation as compared with the more frequent Gln84 variant. Given the key role of AKT in modulating not only insulin signalling but also insulin secretion, it was not surprising that β-cells and human pancreatic islets carrying the Arg84 variant showed also impaired insulin secretion. Also, of note is that in human vein endothelial cells carrying the Arg84 variant showed a reduced insulin-induced nitric oxide release, an established early atherosclerotic step. Accordingly with in vitro studies, in vivo studies indicate that TRIB3 Arg84 is associated with insulin resistance, T2DM and several aspects of atherosclerosis, including overt CVD. In all, several data indicate that the TRIB3 Arg84 variant plays a role on several aspects of glucose homoeostasis and atherosclerotic processes, thus unravelling new molecular pathogenic mechanisms of highly prevalent disorders such as T2DM and CVD.

Original languageEnglish
Pages (from-to)1108-1111
Number of pages4
JournalBiochemical Society Transactions
Volume43
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • Cardiovascular disease
  • Insulin resistance
  • Insulin signaling
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry

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