The Correlation And Molecular Mechanisms Of Pathogenesis Of Resistin In Obese Type 2 Diabetes Rhesus Monkey Models

Objective:Resistin,a hormone-like factors produced by fat cells secrete adipocyte-specific,was a potential target for the treatment of insulin resistance in the type 2 diabetes mellitus (T2DM). Since the gene function and biological characteristics of resistinare were not entirely clear, and there were different results of its biological function on insulin resistance function. Therefore, we chose the rhesus monkeys as our objects to take preliminary exploration on the relationship between the resistance and type 2 diabetes mellitus.Methods:1) The adult rhesus monkeys were fed with high fat/high sucrose diets to be induced as the obese T2DM rhesus monkey models. The level of resistin was detected. After this, we took the correlation analysis between resistin and part of clinical parameters of T2DM and insulin sensitivity.2) We cloned the full-length gene of the macaques" resistin and built recombined vectors with the lentiviral vectors.3) The human hepatoma cells (Huh-7) were infected with the recombined lentiviral vectors and the regulated genes and signal pathways were screened which were caused by resistin in the pathogenesis of T2DM by gene chip technology.Results:1) Analysis of the serum resistin level in T2DM rhesus monkey models induced by high fat diets, revealed that the level of serum resistin in the T2DM group increases obviously (P< 001), and it had a positive correlation with the clinical indicators TC, LDL-C, FPG, FPI, HbAlc and HOMA-IR, but it had a negative relevance with HOMA-β. 2) MacRETN successfully overexpressed mediated by lentiviral vectors in Huh-7 cells. The results of gene chip analysis showed15 genes associated with cAMP signal pathway were regulated by the resistin including IL6 and VIP, which could induce cell apoptosis, promote glycogenolysis, cause inflammation or regulate the insulin senstivity.Conclusion:We speculated resistin closely related to T2DM, which possibly activated the downstream signal pathways inclduding MAPK, ERK and AKT and so on mediated by the second messenger-cAMP to regulate of expression of pro-inflammatory cytokines, apoptosis factor and other genes and then to initiate cell oxidative stress response, inflammatory reaction and apoptosis function.It indicated that resistin in T2DM may negatively participate in and block T2DM glycometabolism process.