Blockade of renin-angiotensin system decreases the incidence of streptozotocin-induced diabetes in rats with long-term high fat diet via inhibiting endoplasmic reticulum stress
- VernacularTitle:替米沙坦通过抑制胰岛内质网应激减少STZ致长期高脂喂养大鼠糖尿病的发生
- Author:
Jin LI
;
Li YUAN
;
Xin LI
;
Hailing LI
;
Suosuo CHENG
- Publication Type:Journal Article
- Keywords:
Renin-angiotensin system;
Endoplasmic reticulum stress;
Diabetes mellitus;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2010;26(1):17-22
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects and mechanisms of renin-angiotensin system (RAS) blockade on pancreatic islet β-cell function in rats with injection of streptozotocin (STZ) and long-term high-fat diet. METHODS: Normal male Wistar rats fed with 16 weeks-long high calorie, and high-fat diet were treated with telmisartan (TI, n=15), and injected with STZ after 24 weeks. One week later, islet function was evaluated by intravenous insulin releasing test (IVIRT). The immunoglobulin binding protein (BIP)/glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP)/growth arrest and DNA-damage-inducible gene 153 (GADD153) mRNA expression levels in the islets were detected by RT-PCR. The expression levels of insulin and Bax protein in the islets were examined by immunohistochemistry. RESULTS: The incidence of diabetes was 80%(12/15)in the high-fat diet+STZ group (HS) and 33% (5/15) in the high-fat diet+STZ+ telmisartan group (TS). Compared to HS group, maximum of insulin secretion in TS group was increased 56.9%. Early insulin secretion index (EISI) and acute insulin response (AIR) were increased by 1.98 times and 0.88 times, respectively. The expression of insulin and insulin positive cell density (PCD) were increased obviously in β-cells. The expression levels of BIP, CHOP and Bax in the islets were decreased significantly. CONCLUSION: Blockade of RAS increases the resistance to streptozotocin-induced diabetes in rats with long-term high-fat diet, and the expression of apoptosis-related molecules is downregulated in endoplasmic reticulum. The mechanism that RAS blockade improves pancreatic islets function and reduces diabetes incidence to some extent may be via attenuating endoplasmic reticulum stress.
