Abstract: Objective To study the effect of exenatide on the expression of ABCA1 and cholesterol metabolism in the pancreas of obese diabetic rats. Methods Twenty- four normal male SD rats and 18 obese diabetic rats (induced by high-fat feeding and STZ injection) were both divided equally into 2 groups for injections of saline or exenatide. After treatment for a week, the expression of ABCA1, cholesterol metabolism, and islet function of the rats were examined using real-time PCR, Western blotting, oil red O staining, cholesterol content determination, and HE staining. Results The expressions of ABCA1 at both mRNA and protein levels in pancreatic tissue were significantly lower in obese diabetic rats than in normal SD rats. The obese diabetic rats showed obvious lipid deposition and increased cholesterol content in the pancreatic tissue with significantly reduced islet volume and structural changes (P<0.05); exenatide treatment of the diabetic rats significantly up-regulated ABCA1 expression, reduced lipid deposition and cholesterol content in pancreatic tissue, and increased number and volume of the islets, which presented with more orderly alignment (P<0.05). Conclusion Obese diabetic rats have lowered ABCA1 expression, cholesterol efflux block, and cholesterol accumulation in the pancreatic tissue. Exenatide can up-regulate ABCA1 expression and promote cholesterol efflux to reduce cholesterol content in the pancreatic tissue and improve islet function in obese diabetic rats.

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