THE NSY MOUSE - A NEW ANIMAL-MODEL OF SPONTANEOUS NIDDM WITH MODERATEOBESITY

The NSY (Nagoya-Shibata-Yasuda) mouse was established as an inbred str ain of mouse with spontaneous development of diabetes mellitus, by sel ective breeding for glucose intolerance from outbred Jcl:ICR mice. NSY mice spontaneously develop diabetes mellitus in an age-dependent mann er. The cumulative incidence of diabetes is 98% in males and 31% in fe males at 48 weeks of age. Neither severe obesity nor extreme hyperinsu linaemia is observed at any age in these mice. Glucose-stimulated insu lin secretion was markedly impaired in NSY mice after 24 weeks of age. In contrast, fasting plasma insulin level was higher in male NSY mice than that in male C3H/He mice (545+/-73 vs 350+/- 40 pmol/l, p < 0.05 , at 36 weeks of age). Pancreatic insulin content was higher in male N SY mice than that in male C3H/He mice (76+/-8 vs 52+/-5 ng/mg wet weig ht, p < 0.05, at 36 weeks of age). Morphologically, no abnormal findin gs, such as hypertrophy or inflammatory changes in the pancreatic isle ts, were observed in NSY mice at any age. These data suggest that func tional changes of insulin secretion in response to glucose from pancre atic beta cells may contribute to the development of non-insulin-depen dent diabetes mellitus (NIDDM) in the NSY mouse. Although insulin sens itivity was not measured, fasting hyperinsulinaemia in NSY mice sugges ts that insulin resistance may also contribute to the pathogenesis of NIDDM. Since these findings are similar to the pathophysiologic featur es of human NIDDM patients, the NSY mouse is considered to be useful f or investigating the pathogenesis and genetic predisposition to NIDDM.