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.
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October 2015
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Review Article|
October 09 2015
The TRIB3 Q84R polymorphism, insulin resistance and related metabolic alterations
Sabrina Prudente;
Sabrina Prudente
1
*Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
1Correspondence may be addressed to either author (emails.prudente@css-mendel.it or Vincenzo.Trischitta@uniroma1.it).
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Vincenzo Trischitta
Vincenzo Trischitta
1
*Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
†Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
‡Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy
1Correspondence may be addressed to either author (emails.prudente@css-mendel.it or Vincenzo.Trischitta@uniroma1.it).
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Publisher: Portland Press Ltd
Received:
May 12 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2015 Authors; published by Portland Press Limited
2015
Biochem Soc Trans (2015) 43 (5): 1108–1111.
Article history
Received:
May 12 2015
Citation
Sabrina Prudente, Vincenzo Trischitta; The TRIB3 Q84R polymorphism, insulin resistance and related metabolic alterations. Biochem Soc Trans 1 October 2015; 43 (5): 1108–1111. doi: https://doi.org/10.1042/BST20150115
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