Pancreatic function of spontaneously diabetic torii rats in pre-diabetic stage.
The Spontaneously Diabetic Torii (SDT) rat is a new model for non-obese type 2 diabetes. In the present study, we investigated changes in insulin secretion from the pancreas of male SDT rats aged 8, 16, and 24 weeks in order to analyze pancreatic function. An analysis of glucose-stimulated insulin secretion (GSIS) in isolated islets showed a marked reduction in insulin secretion in pre-diabetic 16-week-old SDT rats. When the islets were treated with tolbutamide or glucagon-like peptide-1 (7-36) amide (tGLP-1) in the presence of 11.2 mM glucose, however, insulin levels were restored to levels of normal rats. In vivo study, SDT rats exhibited a marked reduction in GSIS from 16 weeks of age. However, tolbutamide or JTP-76209, which is a novel dipeptidyl peptidase IV (DPP IV) inhibitor, increased insulin release after glucose loading and improved glucose tolerance. A marked reduction in GSIS was observed in pre-diabetic SDT rats and the reduction was improved by tolbutamide, tGLP-1, and the DPP IV inhibitor. Therefore, we concluded that the SDT rat is useful, as a model of non-obese insulin secretory disorder, for the analysis of the onset of type 2 diabetes and the development of antidiabetic agents.
Matsui
Kenichi
K
Japan Tobacco Inc., Central Pharmaceutical Research Institute, Murasaki-cho, Takatsuki, Osaka, Japan.
Oda
Tomohiro
T
Nishizawa
Emiko
E
Sano
Ryuhei
R
Yamamoto
Hiromi
H
Fukuda
Sumiaki
S
Sasase
Tomohiko
T
Miyajima
Katsuhiro
K
Ueda
Nobuhisa
N
Ishii
Yukihito
Y
Ohta
Takeshi
T
Matsushita
Mutsuyoshi
M
D000818:Animals; D001120:Arginine; D001565:Benzoates / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology
C545654:2-(4-(amino(N-cyclobutyl-N-methylcarbamoyl)methyl)cyclohexylmethoxymethyl)-5-methylbenzoic acid; D001565:Benzoates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D001120:Arginine; D014044:Tolbutamide; C051322:glucagon-like peptide 1 (7-37)