title: Pancreatic islet beta-cell deficit and glucose intolerance in rats with uninephrectomy.
abstract: This study was performed to examine the effect of chronic renal impairment and renin-angiotensin system (RAS) activation induced by unilateral nephrectomy (UNX) on the development of pancreatic islet beta-cell deficit and glucose intolerance. Sprague-Dawley rats were randomized into three groups: untreated UNX (n=10), UNX treated with the angiotensin-converting enzyme inhibitor lisinopril (n=8) and sham operation (n=10). Blood glucose, serum insulin, renal function and histological changes of kidney and pancreas were examined 8 months postoperation. Compared with the sham rats, UNX rats developed renal impairment, insulin deficiency and glucose intolerance. Histological staining revealed an islet beta-cell deficit associated with increased immunoreactivity for angiotensin and angiotensin type 1 receptor in UNX rats. Treatment with lisinopril significantly improved renal dysfunction, hyperglycemia, insulin secretion and islet RAS expression. These data suggest that chronic renal impairment and RAS activation may contribute to islet beta-cell loss and glucose intolerance. RAS blockade may therefore prevent these disorders.
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin N.T., Hong Kong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sui
authors.forename: H-L
authors.initials: HL
authors.lastname: Zhao
authors.forename: R C W
authors.initials: RC
authors.lastname: Ma
authors.forename: C S
authors.initials: CS
authors.lastname: Ho
authors.forename: A P S
authors.initials: AP
authors.lastname: Kong
authors.forename: F M M
authors.initials: FM
authors.lastname: Lai
authors.forename: H K
authors.initials: HK
authors.lastname: Ng
authors.forename: D K
authors.initials: DK
authors.lastname: Rowlands
authors.forename: J C N
authors.initials: JC
authors.lastname: Chan
authors.forename: P C Y
authors.initials: PC
authors.lastname: Tong
mesh_terms: D000818:Animals; D018149:Glucose Intolerance / Q000209:etiology*; D007328:Insulin / Q000172:deficiency / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D007674:Kidney Diseases / Q000150:complications* / Q000209:etiology / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D007328:Insulin