DESENSITIZATION OF SOMATOSTATIN, TRH AND GHRH RESPONSES TO GLUCOSE INTHE DIABETIC (GOTO-KAKIZAKI) RAT HYPOTHALAMUS

We have studied the effects of glucose on the release of somatostatin (SS), TRH and GHRH from incubated hypothalami of normal and geneticall y diabetic, Goto-Kakizaki (GK) rats. The active isomer D-glucose cause d a dose-related inhibition of SS, TRH and GHRH from normal rat hypoth alami over a 20-min incubation period in vitro. In contrast, in GK rat s the effects of glucose on TRH and SS were significantly reduced and the effects on GHRH were abolished. These data indicate that the sensi tivity of SS-, TRH- and GHRH-producing hypothalamic neurones is reduce d in diabetic rats. The effect is most pronounced for GHRH release as there was no change in the release of this peptide with increasing glu cose concentrations. In conclusion, it appears that the diabetic state in GK rats causes differential desensitisation (GHRH>TRH and SS) of n euronal responses to subsequent changes in glucose concentrations in v itro. This may be due to alterations in the neurotransmitter control a nd/or a reduction in number, affinity or function of glucose transport ers on these peptidergic neurones or other intermediary neuronal pathw ays.