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-Y asuda (NSY) mice, an inbred strain of mice with spontaneous development of type 2 (non-insulin-dependent) diabetes mellitus, the insulin response to g lucose (5.5 to 27.8 mmol/L) and nonglucose stimuli (glibenclamide, arginine , and BayK8644, a Ca-channel opener) was studied in vitro using isolated is lets 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 significa ntly different between NSY and C3H/He mice, but insulin response to a high concentration of glucose (greater than or equal to 11.1 mmol/L) was signifi cantly smaller in NSY mice than in control C3H/He mice. The dose-response c urve of insulin secretion showed a markedly reduced maximum response, but a lmost normal glucose sensitivity in NSY islets. Insulin responses to gliben clamide (1 mmol/L), arginine (20 mmol/L), and BayK8644 (0.1 mmol/L) were al so significantly smaller in NSY mice than in C3H/He mice. Insulin content o f islets, in contrast, was significantly higher in NSY mice than in C3H/He mice. The impaired insulin response to glucose and nonglucose stimuli toget her with higher insulin content in islets in the NSY mouse suggest that a d efect in voltage-dependent Ca2+-channel or thereafter in the cascade of ins ulin secretion may be responsible for impaired insulin secretion in NSY mic e. NSY mice, therefore, could be a novel animal model of type 2 diabetes wi th a defect in insulin secretion at a different site from that in previousl y known animal models. Copyright (C) 2001 by W.B. Saunders Company.