CENTRALLY ADMINISTERED TRH-INDUCED INSULIN-SECRETION IS IMPAIRED IN THE OTSUKA-LONG-EVANS-TOKUSHIMA-FATTY RATS, A MODEL OF SPONTANEOUS NON-INSULIN-DEPENDENT DIABETES-MELLITUS

To investigate whether insulin secretion induced by stimulation of the vagus nerve is preserved or impaired in Otsuka-Long-Evans-Tokushima F atty (OLETF) rats, we injected 10(-8) mol of thyrotropin-releasing hor mone (TRH) into the third cerebral ventricle and determined the serum level of insulin in the unanesthetized, unrestrained rats. Intracerebr oventricular (i.c.v.) injection increased the serum levels of glucose and insulin in both OLETF and Long-Evans-Tokushima-Otsuka (LETO) rats, a nondiabetic control strain, at 8-12 weeks of age. At 24-28 weeks of age, the increased level of glucose in OLETF rats was comparable to L ETO rats but that of insulin was lower than control after the i.c.v. i njection of TRH. Pretreatment with i.v. atropine had no significant ef fect on such hyperglycemia. However, the increases in the serum levels of insulin were suppressed in both OLETF and LETO rats. The plasma le vels of epinephrine, norepinephrine, and glucagon rose significantly a fter TRH. There was no significant difference in the levels of any hor mones between the two groups. In OLETF rats at 24-28 weeks of age, i.v . glucose load induced significantly higher serum levels of glucose an d insulin than LETO rats. The results suggest that the vagus nerve-med iated insulin secretion is impaired in OLETF rats, similar to an auton omic diabetic neuropathy in the early stage of diabetes. This impairme nt may play some role in deteriorating glucose tolerance in this spont aneously developed diabetes model. (C) 1998 Elsevier Science B.V. All rights reserved.