Insulin secretion to glucose as well as nonglucose stimuli is impaired in spontaneously diabetic Nagoya-Shibata-Yasuda mice.

Abstract

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.

• Authors: Y Hamada, H Ikegami, H Ueda, Y Kawaguchi, E Yamato, K Nojima, K Yamada, N Babaya, M Shibata, T Ogihara
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 50 Issue 11 Pg. 1282-5 (Nov 2001) ISSN: 0026-0495 [Print] United States
• PMID: 11699045 (Publication Type: Journal Article)
• Copyright: Copyright 2001 by W.B. Saunders Company

Chemical References

• Blood Glucose
• Calcium Channel Agonists
• Hypoglycemic Agents
• Insulin
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Arginine
• Glucose
• Glyburide

Topics

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (pharmacology)
• Animals
• Arginine (pharmacology)
• Blood Glucose (drug effects)
• Calcium Channel Agonists (pharmacology)
• Cell Separation
• Diabetes Mellitus, Experimental (physiopathology)
• Diabetes Mellitus, Type 2 (physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Glucose (pharmacology)
• Glucose Tolerance Test
• Glyburide (pharmacology)
• Hypoglycemic Agents (pharmacology)
• In Vitro Techniques
• Insulin (analysis, blood, metabolism)
• Insulin Secretion
• Islets of Langerhans (chemistry, metabolism)
• Male
• Mice
• Mice, Inbred C3H
• Mice, Inbred Strains
• Stimulation, Chemical