The Effects And Mechanism Of Telmisartan On Pancreatic β Cells Of Type 2 Diabetic Rats

AimsThe aims of this study were to investigate whether telmisartan had an effect on pancreaticβcells of type 2 diabetic Sprague-Dawley(SD)rats induced by high fat and fructose diet, and to clear the mechanism which telmisartan had the effect on pancreaticβcells of type 2 diabetic SD rats.MethodsMale SD rats were randomly divided into four groups: Standard Chow Diet (SCD) group, High Fat and Fructose Diet (HFFD) group, HFFD with treatment by telmisartan (HFFD+Tel) group and SCD with treatment by telmisartan (SCD+Tel) group. SCD group and SCD+Tel group was fed with standard chow diet for 12 weeks. At the end of fourth week SCD group was began to be administered intragastrically with 0.5 ml physiological saline everyday, while SCD+Tel group with 0.5ml telmisartan physiological saline solution (5mg*kg-1*d-1). HFFD group and HFFD+Tel group was fed with high fat and fructose diet in order to induce type 2 diabetic rats model. At the end of fourth week four groups rats were fasting overnight. Intraperitoneal injection Glucose Tolerance Test (IPGTT) and Insulin Release Test (IRT) was performed. Though comparing with FBG and IPGTT of four groups, it was estimated whether type 2 diabetic rats model were induced successfully. Where after 8 weeks, HFFD group was continue fed with high fat and fructose diet and administered intragastrically with 0.5ml physiological saline everyday, and HFFD+Tel group was also continue fed with high fat and fructose diet and administered intragastrically with 0.5ml telmisartan physiological saline solution (5mg*kg-1*d-1). Fasting Blood Glucose (FBG) and Fasting Serum Insulin (FSI) was measured every two weeks. Insulin Sensitive Index (ISI) was calculated with FBG and FSI. At the end of twelfth week four groups rats were fasting overnight. IPGTT was performed to analyze insulin sensitivity. IRT was performed to evaluate function of pancreaticβcells. Body weight and pancreatic tissue weight of SD rats were measured, One part of pancreatic tissue was fixed by 10% formaldehyde. Islet morphology was assessed by haematoxylin and eosin staining to observe the structure of pancreas. Immunohistochemistry with anti-rat insulin and anti-rat NFκBp65 antibody was performed to observe the expression of insulin and NFκBp65 protein in pancreatic tissue. Reverse Transcription Polymerase Chain Reaction (RT-PCR) was performed to test the level of Peroxisome proliferator-activated receptorγ(PPARγ), Glucose transporter 2 (Glut 2), Insulin 1(Ins 1),Pancreatic and Duodenal Homeobox 1(PDX-1)mRNA in pancreatic tissue.Results(1) Comparing with SCD group, the level of FBG and FSI of HFFD group heightened, Insulin Sensitive Index (ISI) dropped, glucose tolerance impaired, at the end of twelfth week the first phase of insulin secreting disappeared, the serum triglyceride and total cholesterol increased, High Density Lipoprotein Cholesterol decreased significantly. The ratios of pancreatic tissue weight to body weight decreased. The structure of pancreas of HFFD group arranged disorderly. Vascular remodeling of pancreas of HFFD group was found obviously. The number ofβcells of HFFD group decreased. The level of Glut 2, Ins 1, PPARγ, and PDX-1 mRNA in pancreas tissue of HFFD group decreased. The level of NFκBp65 protein of islet of HFFD group increased.(2) Comparing with HFFD group, the level of FBG and FSI of HFFD+Tel group decreased significantly, ISI elevated, glucose clearance improved, at the end of twelfth week the first phase of insulin secreting existed, the serum triglyceride and total cholesterol decreased, High Density Lipoprotein Cholesterol increased significantly. The ratios of pancreatic tissue weight to body weight increased. The structure of pancreas of HFFD+Tel group arranged orderly. Vascular remodeling of pancreas of HFFD+Tel group was seldom found. The number ofβcells of HFFD+Tel group increased. The level of Glut 2, Ins 1, PPARγ, and PDX-1 mRNA in pancreas tissue of HFFD group increased. The level of NFκBp65 protein of islet of HFFD+Tel group decreased.Conclusion(1) Telmisartan can lower FBG and FSI, increase ISI, improve glucose tolerance, and ameliorate insulin resistance of type 2 diabetic rats.(2) Telmisartan may protect the function of pancreaticβcells and vascular of pancreas through decreasing FSG, regulating blood fat, increasing the level of Glut 2, Ins 1, PPARγ, and PDX-1 mRNA of pancreas, decreasing the level of NFκBp65 protein of pancreas, and decreasing vascular remodeling of pancreatic tissue..