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.

eticulum stress.

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell was decreased significantly; the relative content of VEGF was increased obviously [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function,diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE,n=10) or valsartan (AR,n=10),the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC,n=10),the area under the curve for insulin from 0 to 30 min (AUCI0-30) of diabetes group (DM,n=8) was decreased by 66.3%;the insulin relative concentration (IRC) of βcell was decreased significantly;the relative content of VEGF was increased obviously [(-4.21±0.13) vs (-4.06±0.29)];MVD in islets was decreased by 71.4%;the relative expression of HIF-1α mRNA was increased by 1.19 times (all P＜0.01). Compared with DM group,the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively;IRC was also increased significantly;the relative content of VEGF was decreased by 21.2% and 21.7% respectively;MVD was increased by 62.5% and 75.0% respectively;the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively (all P＜0.01 or P＜0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.