Insulin secretion to glucose as well as nonglucose stimuli is impaired in spontaneously diabetic Nagoya-Shibata-Yasuda mice.
To clarify the mechanisms of impaired insulin secretion in Nagoya-Shibata-Yasuda (NSY) mice, an inbred strain of mice with spontaneous development of type 2 (non-insulin-dependent) diabetes mellitus, the insulin response to glucose (5.5 to 27.8 mmol/L) and nonglucose stimuli (glibenclamide, arginine, and BayK8644, a Ca-channel opener) was studied in vitro using isolated islets from male NSY and control C3H/He mice at 36 weeks of age by the batch incubation method. Insulin response to 5.5 mmol/L glucose was not significantly different between NSY and C3H/He mice, but insulin response to a high concentration of glucose (> or = 11.1 mmol/L) was significantly smaller in NSY mice than in control C3H/He mice. The dose-response curve of insulin secretion showed a markedly reduced maximum response, but almost normal glucose sensitivity in NSY islets. Insulin responses to glibenclamide (1 mmol/L), arginine (20 mmol/L), and BayK8644 (0.1 mmol/L) were also significantly smaller in NSY mice than in C3H/He mice. Insulin content of islets, in contrast, was significantly higher in NSY mice than in C3H/He mice. The impaired insulin response to glucose and nonglucose stimuli together with higher insulin content in islets in the NSY mouse suggest that a defect in voltage-dependent Ca(2+)-channel or thereafter in the cascade of insulin secretion may be responsible for impaired insulin secretion in NSY mice. NSY mice, therefore, could be a novel animal model of type 2 diabetes with a defect in insulin secretion at a different site from that in previously known animal models.
Hamada
Y
Y
Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Ikegami
H
H
Ueda
H
H
Kawaguchi
Y
Y
Yamato
E
E
Nojima
K
K
Yamada
K
K
Babaya
N
N
Shibata
M
M
Ogihara
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D013268:Stimulation, Chemical
D001786:Blood Glucose; D002120:Calcium Channel Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001120:Arginine; D005947:Glucose; D005905:Glyburide