title: Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus.
abstract: The aim of this study is to determine the antidiabetic activity of Ang-(1-7), an important component of the renin-angiotensin system, in a rat model of streptozotocin (STZ)-induced type 2 diabetes mellitus (DM). A total of 36 male Wistar rats were randomly divided into 3 groups: control group fed standard laboratory diet, DM group fed high-fat diet and injected with STZ, and Ang-(1-7) group receiving injection of STZ followed by Ang-(1-7) treatment. Body weight, blood glucose levels, fasting serum Ang II and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The pancreas was collected for histological examination and gene expression analysis. Notably, the Ang-(1-7) group showed a significant decrease in fasting blood glucose and serum Ang II levels and HOMA-IR values and increase in fasting serum insulin levels. Pancreatic β cells in the control and Ang-(1-7) groups were normally distributed in the center of pancreatic islets with large clear nuclei. In contrast, pancreatic β cells in the DM group had a marked shrinkage of the cytoplasm and condensation of nuclear chromatin. Ang-(1-7) treatment significantly facilitated insulin production by β cells in diabetic rats. The DM-associated elevation of inducible nitric oxide synthase (iNOS), caspase-3, caspase-9, caspase-8, and Bax and reduction of Bcl-2 was significantly reversed by Ang-(1-7) treatment. Taken together, Ang-(1-7) protects against STZ-induced DM through improvement of insulin resistance, insulin secretion, and pancreatic β cell survival, which is associated with reduction of iNOS expression and alteration of the Bcl-2 family.
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: 13007000339@163.com.
authors.forename: Junhua
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Huilu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: 15333665668@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051017:Apoptosis Regulatory Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Angiotensin (1-7); Cell apoptosis; Islet function; Oxidative stress; Type 2 diabetes mellitus