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The Effect of Ang(1-7)/MAS Pathway on Pancreatic Islet Microcirculation and Function in Rat with Long-term High-fat Diet

Author: LiGuangLi
Tutor: YuanLi
School: Huazhong University of Science and Technology
Course: Internal Medicine
Keywords: Angiotensin-(1-7 ) Islet function Insulin Resistance Islet endothelial function Pancreatic microcirculation
CLC: R587.1
Type: Master's thesis
Year: 2011
Downloads: 14
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Objective Ang (1-7) and the MAS receptor blocking agent A-779 intervention long-term high-fat high-calorie feeding induced insulin resistant rats, observed Ang (1-7) / MAS pathway of islet endothelial cells, islet microcirculation and islet function, and to investigate the regulatory role of long-term high-fat induced islet β-cell dysfunction and related mechanisms. 80 male Wistar rats basic feed adaptive feeding two weeks, 20 were randomly selected as the normal control group (NC group, n = 20), given the normal diet, the remaining 60 rats high fat and high calorie diet feeding randomly divided into high-fat group (H0, n = 20) after 12 weeks, the intervention group of Ang-(1-7) (H1 group, n = 20), Ang (1-7) A-779 intervention group (H2, n = 20) were treated with saline, Ang-(1-7), Ang-(1-7) A-779 subcutaneous injection four weeks, the intervention dose of Ang-(1-7) and A-779 are 300μg · kg -1 · d -1 . The colored microspheres Technology (sedimentation) detection of pancreatic microcirculation blood flow; immunofluorescence assay islet of vWF (von Willebrand factor) expression and relative insulin content in pancreatic β-cells (insulin relative concentration IRC); RT-PCR assay islet endothelial cell markers mRNA expression levels of vWF (von Willebrand factor); intravenous glucose tolerance test (IVGTT) and intravenous insulin release the test (IVIRT) detection reflect β-cell function. The results compared with the NC group, the the H0 group of the glucose infusion rate (GIR) decreased by 32% [(5.19 ± 0.81 vs 7.65 ± 0.45) mg · kg -1 · min -1 -1 · min -1 P lt; 0.05); give Ang (1-7) after the intervention, compared with H0, H1 rats glucose infusion rate (GIR) increased 29% (6.72 ± 0.39 vs 5.19 ± 0.81) mg · kg 17.52 vs 42.25 ± 14.39, P lt; 0.05), immunofluorescence results showing the amount of β-cell insulin expression was significantly higher (P lt; 0.05), pancreas micro-circulation blood flow increased 46% [(0.866 ± 0.110 vs 0.595 ± 0.062) vs 13.8 ± 2.21 P lt; 0.05), microvascular density was significantly increased, the islet vWFmRNA expression levels of 35% (P lt; 0.05); give MAS receptor blocker, compared with H1, H2 glucose infusion rate , acute insulin secretion response (AIR) decreased 23% (50.60 ± 14.39 vs 65.65 ± 17.52, P lt; 0.05), β-cell insulin expression amount substantially significantly lower (P lt; 0.05), pancreatic micro-circulation of blood flow to reduce by 35% [ % (relative concentrations were 14.4 ± 2.85 vs 19.3 ± 3.16 P lt; 0.05), islets vWFmRNA expression levels decreased 15% (P lt; 0.05). Conclusion Long-term high-fat high-calorie feeding-induced insulin resistance in rats the pancreatic microcirculation perfusion decreased slightly, the islet microcirculation the decompensated performance: endothelial cell dysfunction, reduced microvessel density. Ang (1-7) combined to improve the islet endothelial function mediated through its receptor MAS islet microcirculation, thus improving the long-term high-fat high-calorie diet rat islet function.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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