| ObjectiveTo induce diabetic rats by high fat high caloric laboratory chow plus intraperitoneal injection of streptozotocin, observe the impact of perindopril and valsartan on the morphology and function of pancreatic islet cells in diabetic rats, and to investigate the protective mechanisms of renin-angiotensin system blockade on the islets in diabetic rats.MethodsDiabetic rats were induced by high fat high caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin(30mg/kg). 32 diabetic rats were divided into normal contrast group (N=10), diabetic group (N=10), perindopril treated group (N=11) and valsartan treated group (N=11). The last two groups were given perindopril (4mg*kg-1*d-1) or valsartan (40mg*kg-1*d-1) treatment for eight weeks, respectively. To detect the islet function by intravenous glucose tolerance test and intravenous insulin release test, islet morphology and intra-islet insulin and transforming growth factors-β1(TGF-β?1) expression by immunohistochemistry, apoptosis of islet cells by TUNEL, proinsunlin mRNA by RT-PCR.ResultsThe plasma glucose in normal contrast group was normal, and plasma insulin climbed to as 4-5 folds as basic level after glucose load, in whom the islets structure was regular, with a large number of insulin-secreting cells and low-grade fibrosis. Compared to normal contrast group, pancreatic islet function in diabetic group was impaired obviously. First-phase insulin secretion expressed as the incremental area under the curve of insulin in the first 10min was reduced by 67% (P<0.01). Most islets were enlarged with disarrayed islet architectures, and insulin relative concentration dropped obviously. The intraislet cell relative volume was decreased by 68% (P<0.01), andβcell nuclear density was decreased by 49% (P<0.01). TGF-β1 relative concentration was increased significantly (P<0.05), and the relative cells volume expressing TGF-β?1 had a 1.52 fold increase (P<0.01). The relative amount of apoptosis cells within islet was increased by 2.14 folds. The intraislet proinsulin mRNA was decreased by 31% (P<0.01). Compared to diabetic group, first-phase insulin secretion in perindopril treated group and valsartan treated group were increased by 41% (P<0.01) and 33% (P<0.01), respectively. Islet architectures were nearly regular, insulin relative concentration were increased to a normal level, and the intraisletβcell relative volumes were increased by 84% (P<0.01) and 76% (P<0.01). In addition,βcell nuclear density in perindopril treated group was increased by 27% (P<0.05). The relative cells volume expressing TGF-β?1were decreased by 44% (P<0.01) and 36% (P<0.01), respectively. The relative amount of apoptosis cells within islet was decreased by 29% (P<0.01) and 36% (P<0.01). And proinsulin mRNA were increased by 23% (P<0.01) and 22% (P<0.01), respectively.ConclusionDiabetic rats could be induced by high fat high caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin, in which islets fibrosis increase,βcell quantity decrease and the ability of insulin secretion was impaired. Renin-angiotensin system blockade could improve the islet morphology of diabetic rats, decrease fibrosis and apoptosis, increaseβcell mass and insulin reserve in endochylema, increase the insulin synthesis ofβc?ells, and improve pancreatic islet function.
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