title: Olmesartan and temocapril prevented the development of hyperglycemia and the deterioration of pancreatic islet morphology in Otsuka-Long-Evans-Tokushima Fatty rats.
abstract: We investigated the impact of olmesartan and temocapril on pancreatic islet beta-cells during the development of diabetes mellitus using Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats. Four-week-old male OLETF rats were fed standard chow (untreated:n5), or chow containing either 0.005% olmesartan(n5) or 0.01% temocapril (n5) until being sacrificed at 35 weeks of age. Pancreas sections were double-stained with anti-insulin and anti-glucagon antibodies. The percent areas of beta-cells, alpha-cells and non-alpha-non-beta-cells were compared among groups. In untreated OLETF rats, the fasting plasma glucose (FPG) level was elevated at the 18th week and remained elevated until the 35th week. On the other hand, no significant elevation in FPG levels was observed in olmesartan- or temocapril-treated rats. Pancreatic islets from olmesartan-treated rats were significantly smaller in size as compared with those from untreated OLETF rats. Furthermore, the average area occupied by beta-cells as a fraction of the total area of an individual islet was significantly higher in olmesartan- or temocapril-treated rats than that in untreated OLETF rats. Olmesartan and temocapril both prevented the development of hyperglycemia, possibly through the prevention of islet beta-cell loss in spontaneously diabetic OLETF rats.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kaihara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Taro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Haruhito A
authors.initials: HA
authors.lastname: Uchida
authors.forename: Hisanao
authors.initials: H
authors.lastname: Norii
authors.forename: Hisanao
authors.initials: H
authors.lastname: Norii
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hanayama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002096:C-Peptide / Q000652:urine; D019270:Fructosamine / Q000097:blood; D006943:Hyperglycemia / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis; D013777:Tetrazoles / Q000627:therapeutic use*; D013841:Thiazepines / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002096:C-Peptide; D007093:Imidazoles; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013841:Thiazepines; D019270:Fructosamine; C055603:temocapril hydrochloride; C437965:olmesartan