Abstract
Type 2 diabetes is caused by defects in both insulin signaling and insulin secretion. Though the role of the ubiquitin proteasome system (UPS) in the pathogenesis of type 2 diabetes remains largely unexplored, the few examples present in the literature are interesting and suggest targets for drug development. Studies indicate that insulin resistance can be induced by stimulating the degradation of important molecules in the insulin signaling pathway, in particular the insulin receptor substrate proteins IRS1, IRS2 and the kinase AKT1 (Akt). In addition, a defect in insulin secretion could occur due to UPS-mediated degradation of IRS2 in the β-cells of the pancreas. The UPS also appears to be involved in regulating lipid synthesis in adipocytes and lipid production by the liver and could influence the development of obesity. Other possible mechanisms for inducing defects in insulin signaling and secretion remain to be explored, including the role of ubiquitylation in insulin receptor internalization and trafficking.Republished from Current BioData's Targeted Proteins database (TPdb; ).
Highlights
The global incidence of diabetes mellitus is increasing at such a rate as to be characterized as an epidemic. This is primarily due to changes in lifestyle that have led to obesity, a major risk factor for diabetes
Levels of blood glucose are normally maintained within a tight range of around 3.6–6.0 mM
GTR4 is primarily expressed in skeletal muscle and adipose tissue [4]
Summary
The global incidence of diabetes mellitus (commonly referred to as diabetes) is increasing at such a rate as to be characterized as an epidemic. Recent findings indicate that insulin stimulates the phosphorylation of one of these transcriptional activators, TORC2, and this phosphorylation leads to its ubiquitylation and targeting for degradation by the COP1 ubiquitin protein ligase [39] Another possible mechanism for modulating insulin signaling is through the regulation of insulin receptor trafficking. The most striking observations of these investigations are that the UPS has a role in downregulating IRS proteins and thereby contributing to the two main defects in diabetes, insulin resistance and impaired insulin secretion Reversing these effects could be a novel approach in the treatment of diabetes and might be tested using gene inactivation models of the SOCS1 and SOCS3 proteins. EGF: epidermal growth factor; HGF: hepatocyte growth factor; iNOS: nitric oxide synthase; IRS: insulin receptor substrate; LDL: low density lipoprotein; PDGF: platelet derived growth factor; SOCS: suppressor of cytokine signaling; VLDL: very low density lipoprotein
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
