Aim: To assess the effects and mechanisms of the action of resistin on basal and insulin‐stimulated glucose uptake in rat skeletal muscle cells. Methods: Rat myo‐blasts (L6) were cultured and differentiated into myotubes followed by stimulation with single commercial resistin (130 ng/mL, 0‐24 h) or cultured supernatant from 293‐T cells transfected with resistin‐expressing vectors (130 ng/mL, 0‐24 h). Liquid scintillation counting was used to quantitate [3H] 2‐deoxyglucose uptake. The translocation of insulin‐sensitive glucose transporters GLUT4 and GLUT1, synaptosomal‐associated protein 23 (SNAP23) and GLUT protein content, as well as the tyrosine phosphorylation status and protein content of insulin receptor substrate (IRS) ‐1, were assessed by Western blotting. Results: Treatment of L6 myotubes with single resistin or cultured supernatant containing recombinant resistin reduced basal and insulin‐stimulated 2‐deoxyglucose uptake and impaired insulin‐stimulated GLUT4 translocation. While SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. Resistin also diminished insulin‐stimulated IRS‐1 tyrosine phosphorylation levels without affecting its protein content. The effects of recombinant resistin from 293‐T cells transfected with resistin‐expressing vectors were greater than that of single resistin treatment. Conclusion: Resistin regulated IRS‐1 function and decreased GLUT4 translocation and glucose uptake in response to insulin. The downregulated expression of SNAP23 may have been partly attributed to the decrease of glucose uptake by resistin treatment. These observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes related to obesity.
BackgroundIt has been demonstrated that vitamin D receptor (VDR), a key gene in the metabolism of vitamin D (VD), may affect the development of Non-alcoholic fatty liver disease (NAFLD) by regulating VD level and its biological effects.ObjectivesTo investigate the effects of serum VD level, VDR variation, and a combination of VDR SNP and environmental behavior factor on the risk of NAFLD.MethodsA total of 3023 subjects from a community in Nanjing were enrolled, including 1120 NAFLD cases and 1903 controls. Serum 25(OH)D3 levels were measured and eight single nucleotide polymorphisms (SNPs) in VDR gene were genotyped.ResultsLogistic regression analyses indicated that VD sufficiency and VD insufficiency were significantly associated with a low risk of NAFLD (all P<0.05; all Ptrend<0.05, in a locus-dosage manner). After adjusting for gender and age, VDR rs2228570-A and rs11168287-A alleles were all reduced the risk of NAFLD (all PFDR=0.136, in dominant model; Ptrend =0.039, combined effects in a locus-dosage manner). The protective effects of two favorable alleles were more evident among subjects ≤40 years, non-hypertension, non-hyperglycemia and non-low high density lipoprotein-cholesterol (all P<0.05). The area under the receiver operating curve of the combination of VDR SNP and exercise time for assessing NAFLD risk was slightly higher than that of only including exercise time or neither (all P<0.05).ConclusionHigh serum VD levels and VDR variants (rs2228570-A and rs11168287-A) might contribute to a low risk of NAFLD in Chinese Han population. The inclusion of VDR SNP and exercise time could improve the efficiency in assessment of NAFLD risk, which might provide a novel perspective for early screening and preventing NAFLD.
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