SIRT6 as a potential target for treating insulin resistance

Publication date: Available online 11 June 2019Source: Life SciencesAuthor(s): Wei Tang, Yingying FanAbstractAimsWe aimed to explore the role of SIRT6 in Insulin resistance (IR). We are the first to investigate on this crucial relationship in an obese mouse model fed on a high-fat diet (HFD) and an IR model based on the mature 3T3-L1-derived adipocytes.Main methodsWestern blotting (WB) and qPCR analysis were performed to evaluate the SIRT6 protein and mRNA expressions in HFD mice as well as IR cells. Injection of adenovirus encoding SIRT6 gene in HFD mice and transfection of pcDNA3-SIRT6 in IR cells increased the glucose uptake levels and insulin sensitivity.Key findingsThe positive regulatory effects of SIRT6 on transient receptor potential vallinoid 1 (TRPV1) in IR cells were confirmed by a mechanistic investigation at both protein and mRNA levels. Further, the overexpression of SIRT6 was found to activate the TRPV1/Calcitonin gene-related peptide (CGRP) signaling and upregulate the glucose transporter (GLUT) expression at protein and mRNA levels. Additionally, administration of the TRPV1 antagonist, SB-705498 repressed the insulin sensitivity upregulated by SIRT6 overexpression accompanied with the inhibition of CGRP and decrease in GLUT proportions. The results also showed that TRPV1 agonist, Capsaicin boosted the SIRT6-induced glucose uptake, CGRP production, and GLUT4 levels.SignificanceOverall, SIRT6 was concluded to be involved in the TRPV1-CGRP-GLUT4 signaling axis t...
Source: Life Sciences - Category: Biology Source Type: research