Blockade of renin angiotensin system increased resistance to STZ-induced diabetes in rats with long-term high-fat diet.

Abstract

This study aimed to investigate whether rennin-angiotensin system (RAS) blockade through telmisartan would increase the resistance to streptozotocin- (STZ-) induced diabetes in insulin resistance rats. There were sixty Wistar rats that were divided into four groups: normal control (NC), high-fat diet (HF), high-fat diet plus STZ injection (HF+S), and high-fat diet plus STZ injection and telmisartan intervention (HF+S+T). Five rats were chosen randomly and respectively from groups NC and HF to undergo a hyperinsulinemic euglycemic clamp. Another five rats were selected randomly from the four groups, respectively, for intravenous injection insulin releasing test (IVIRT), and the other five rats for pancreas specimens used in islet cell immunohistochemistry staining (stained for insulin, NF-κB, and caspase-3), islet cell apoptosis staining, and reverse transcription PCR (AT1R and IL-1 beta). There was a significant difference of overt diabetes incidence between groups HF+S+T and HF+S (P < 0.05). Furthermore, inflammatory markers and islet cell apoptosis were found to be significantly reduced in group HF+S+T compared with group HF+S (all P < 0.01 or P < 0.05). Overall, telmisartan-treated rats were found to have reduced RAS activity, increased resistance to STZ-induced diabetes, reduced inflammatory markers, and improvement of islet cell function and morphology.