title: Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet.
abstract: Insulin therapy has been shown to contribute to extended glycemia remission in newly diagnosed patients with type 2 diabetes mellitus. This study investigated the effects of insulin treatment on pancreatic lipid content, and β-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on β-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic β-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative β-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet β-cell secreting function was assessed by the index ΔI30/ΔG30. Glucose-intolerant rats had higher pancreatic lipid content, more islet β-cell apoptosis, lower β-cell proliferation, and reduced β-cell area in pancreas when compared with controls. Insulin therapy reduced blood glucose, inhibited pancreatic lipid accumulation and islet β-cell apoptosis, and increased β-cell proliferation and β-cell area in glucose-intolerant rats. Furthermore, impaired insulin secretion and insulin production in glucose-intolerant rats were improved by insulin therapy. Insulin can preserve β-cell function by protecting islets from glucotoxicity and lipotoxicity. It can also ameliorate β-cell area by enhancing β-cell proliferation and reducing β-cell apoptosis.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui-qing
authors.initials: HQ
authors.lastname: Li
authors.forename: Bao-ping
authors.initials: BP
authors.lastname: Wang
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Deng
authors.forename: Jiao-yue
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yong-bo
authors.initials: YB
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.forename: Wen-fang
authors.initials: WF
authors.lastname: Xia
authors.forename: Tian-shu
authors.initials: TS
authors.lastname: Zeng
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Chen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood / Q000378:metabolism; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D007328:Insulin / Q000032:analysis / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014280:Triglycerides / Q000032:analysis / Q000097:blood / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D013311:Streptozocin