ALTERATIONS OF INSULIN AND GLUCAGON-SECRETION FROM THE PERFUSED PANCREAS BEFORE, AT THE ONSET AND AFTER THE DEVELOPMENT OF DIABETES IN MALEOTSUKA LONG-EVANS TOKUSHIMA FATTY (OLETF) RATS

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an obese non-insu lin dependent diabetes mellitus (NIDDM) model of an inbred strain. In this study, basal (2.8 mM glucose) insulin and glucagon and their resp onses to glucose (16.7 mM) were examined at the age of 9 weeks (n = 3) before the onset of diabetes, at 23 weeks (n = 6) at the onset of dia betes, and at 48 weeks (n = 5) after the development of diabetes by pa ncreatic perfusion. In Long-Evans Tokushima Otsuka (LETO, control) rat s, insulin responses to glucose showed a biphasic pattern at all three ages, while in OLETF rats, basal insulin concentrations were signific antly increased compared to those in controls at the age of 9 and 48 w eeks. Insulin responses to glucose showed no difference from controls at 9 and 23 weeks, however, at 48 weeks the response was significantly decreased. In controls, high basal glucagon concentrations showed sig nificant decrease in response to glucose at all ages. In OLETF rats, b asal glucagon concentrations showed significant decrease compared to t hose in control rats at 23 and 48 weeks. Glucagon response to glucose significantly decreased at 9 and 23 weeks, but at 48 weeks there was n o change in concentration in response to glucose. Pancreatic insulin c ontent was lower at 48 weeks in OLETF rats than in LETO rats, although no differences were observed at other ages. There were no significant differences in pancreatic glucagon content between the two groups at any age. Morphologically, in OLETF rats the number of pancreatic B cel ls were decreased and A cells migrated into the center of islets at 48 weeks. The results suggested that one of the causes of diabetes in OL ETF rats is impaired insulin response to glucose. (C) 1997 Elsevier Sc ience Ireland Ltd.