Effect Of Exenatide On Lipid Metabolism And Adipokines Expression Of Adipose Tissue In Diabetic

PART1Title:Effect of exenatide on lipid metabolism of adipose tissue in diabetic ratsObjective:To investigate the mechanisms of exenatide and insulin glargine in regulating lipid metabolism of adipose tissue in diabetic rats.Methods:Male SD rats (7-8 weeks old,180-200g) were randomly divided into normal chow (NC, n=8) or high-fat diet (n=30). After 5 weeks of high-fat diet, diabetic rats were induced by low dose streptozotocin (STZ) and were randomly divided into 3 groups:untreated diabetic group (DM), exenatide-treated group (EXE) or insulin glargine-treated group (INS). NC and DM groups were administrated by normal saline, the other two groups were given exenatide or insulin glargine for 4 weeks initiated at the 3rd day after STZ injection. Protein expressions of phosphoenolpyruvate carbexykinase (PEPCK) and fatty acid synthase (FAS) were assayed by western blot. Gene expressions of PEPCK, FAS, acetyl-coA carboxylasel (ACC1), pigment epithelium-derived factor (PEDF), and adipose triglyceride lipase (ATGL) were quantified by real-time PCR. ANOVA or LSD test were used for data analysis.Results:Compared with NC, the gene and protein levels of PEPCK, FAS, and ACC1 in DM group were significantly decreased (all P<0.05), while the gene expressions of ATGL and PEDF were increased (all P<0.05). After exenatide and insulin glargine treatment, mRNA and protein levels of PEPCK, FAS, and ACC1 were increased (all P<0.05), and mRNA levels of ATGL and PEDF were decreased (all P<0.05). Compared with INS group, the increases in the gene and protein levels of PEPCK and FAS in EXE group were greater (all P<0.05).Conclusions:Our results suggested that exenatide and insulin glargine treatment can ameliorate ectopic lipid deposition by increasing lipid synthesis and decreasing lipolysis of adipocytes in diabetic rats, in which exenatide has greater effect on triglyceride synthesis.PART 2Title:Effect of exenatide on adipokines expression of adipose tissue in diabetic ratsObjective:To investigate the mechanisms of exenatide and insulin glargine in regulating adipokines expression of adipose tissue in diabetic rats.Methods:Male SD rats (7-8 weeks old,180-200g) were randomly divided into normal chow (NC, n=8) or high-fat diet (n=30). After 5 weeks of high-fat diet, diabetic rats were induced by low dose streptozotocin (STZ) and were randomly divided into 3 groups:untreated diabetic group (DM), exenatide-treated group (EXE) or insulin glargine-treated group (INS). NC and DM groups were administrated by normal saline, the other two groups were given exenatide or insulin glargine for 4 weeks initiated at the 3rd day after STZ injection. Protein expressions of tumor necrosis factor α (TNF-α) was assayed by western blot. Gene expressions of TNF-α, interleukin-6 (IL6), interleukin-1β (IL1β), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor type-1 (PAI-1) and adiponectin were quantified by real-time PCR. ANOVA or LSD test were used for data analysis.Results:Compared with NC, the gene and protein levels of TNF-α, IL6, MCP-1 and PAI-1 in DM group were significantly increased (all P<0.05), while the gene expressions of adiponectin was decreased (P<0.05). After exenatide and insulin glargine treatment, mRNA and protein levels of TNF-α, IL6, MCP-1 and PAI-1 were decreased (all P<0.05), and mRNA levels of adiponectin were increased (all P<0.05). Compared with INS group, no significant difference between the two groups. Exenatide and insulin glargine failed to affect the gene levels of ILl β (all P>0.05).Conclusions:Our results suggested that exenatide and insulin glargine treatment can reduce proinflammatory adipokines levels, and increase the expression of adiponectin. And there is no significant difference between the two groups.