Activation Of Angintensin Type Ⅱ Type 2 Receptors Protects Islets β Cells In Diet-Induced Obesity Rats

ObjectiveWe evaluated the effect that Angiotensin Ⅱ type 2 receptors (AT2R) stimμLated by compound C21 on islets of rats fed high-fat diet.Methods90 adult male Sprague-Dawley (SD) rats were randomly divided into two groups: the control group (fed with normal diet, n=10) and the experimental group (fed with high-fat diet, n=80). Two weeks after feeding, obesity-resistant rats were excluded from the experimetal group. Nine weeks after feeding, obese rats in the experimental group were assighed to four treatment groups:HFD, HFD+ARB, HFD+C21, HFD+C21+ARB. C21 and telmisartan were given by intragastric administration for one month, lmg/kg/d, and high-fat diet was continually afforded during treatment. Body weight (BW) was measured weekly. After thirteen weeks, Body weight, body length, Lee’s index, fasting blood glucose (FBG), serum lipids, glucose tolerance, protein and mRNA expression related to insuin secretion, area size of pancreas islet and (3 cells were observed. Comparison was performed between each experimental group and the control group.Results1. The HF group demonstrated a higher body weights than the normal group and there were no differences in body weights among treatment groups; Except for HDL-C, TC、TG、LDL-C in all the high-fat feeding groups were significantly higher than normal group, but with no obvious difference among treatment groups.2. IPGTT result was higher in the HFD group and HF+ARB group compared to the normal group. Compared to the HFD group, blood glucose showed a significant lower in the HFD+C21 group and HFD+C21+ARB group; IPITT result showed each point of the blood glucose level in the experiment groups displayed a higher as compared with the normal group, but there was no difference in treatment groups.3. The fasting insulin level of rats in HFD+C21 treatment group and HFD+C21+ARB treatment group showed a significant increase as compared with rats in the other groups; HFD group and HF+ARB group had a lower HOMA-P compared to normal group, and the HOMA-βin the HFD+C21 group and HFD+C21+ARB group were higher than HFD group and HFD+ARB group; Compared to the rats in the normal group, the rats in the high-fat feeding groups displayed a significantly higher HOME-IR, with no difference in treatment groups.4. HFD+C21+ARB and HFD+ARB treatment improved the protein and mRNA expression of the pancreatic islets GLUT2, PDX1, GCK. Compared to HFD group, area size of pancreas islet and β cells in the treatment groups showed a smaller.ConclusionsActivation of Angiotension type 2 receptor can reduce the blood glucose of diet-induced obesity rats, increase the protein and mRNA expression of the pancreatic islets GLUT2, PDX1, GCK, promote the secretion of insulin, and improve area size of pancreas islet and β cells, but no obvious effect of insulin sensitivity.