title: Oxidative stress increases the risk of pancreatic β cell damage in chronic renal hypertensive rats.
abstract: Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two-kidney, one-clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α-lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed. In addition, insulin secretion from islet cells was measured. OGTT yielded abnormal results, and the number of islet cells and the size of pancreatic β/α cells were decreased in 2K1C rats. Basal insulin levels were also reduced in the plasma. Insulin secretion from pancreatic islet cells in response to high glucose was also attenuated in 2K1C rats compared with sham rats. The levels of oxidative stress markers, including 8-hydroxydeoxyguanosine and NADPH oxidase-4, were increased in pancreatic tissue and pancreatic islets in 2K1C rats. The abnormalities observed in 2K1C rats were improved by captopril or α-lipoic acid treatment. These findings indicate that sustained renal hypertension may lead to pancreatic dysfunction, increasing oxidative stress in pancreatic islets.
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea Department of Pharmacology, Taishan Medical University, Shandong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Byung M
authors.initials: BM
authors.lastname: Park
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Seung A
authors.initials: SA
authors.lastname: Cha
authors.affiliation: Department of Biochemistry, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Ui J
authors.initials: UJ
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Byung H
authors.initials: BH
authors.lastname: Park
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Woo H
authors.initials: WH
authors.lastname: Park
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea shkim@chonbuk.ac.kr.
authors.forename: Suhn H
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D002216:Captopril / Q000008:administration & dosage* / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000662:veterinary; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000662:veterinary; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D007328:Insulin; D000804:Angiotensin II; D008063:Thioctic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002216:Captopril; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D003849:Deoxyguanosine
keywords: 8‐hydroxydeoxyguanosine; H2O2; NADPH oxidase‐4; advanced glycation end products; angiotensin II; diabetes; hypertension; oxidative stress; β cell