Functional characterization of alpha-adrenoceptors on pancreatic islets of fa/fa Zucker rats.

Recently, a defect in pertussis toxin-independent actions of epinephrine on pancreatic B-cells of fa/fa Zucker rats was reported (Cawthorn and Chan (1991) Mol. Cell. Endocrinol. 75, 197-204). We now report studies of islet alpha 2-adrenoceptor function of fa/fa rats. Insulin and cAMP production by islets of obese rats were both inhibited by the alpha 2-adrenoceptor agonist clonidine. Calculated pD2 values for clonidine were 9.57 +/- 0.59 and 9.43 +/- 0.33 for lean and fa/fa rat islets, respectively. Yohimbine reversed clonidine effects equipotently in lean and obese rat islets (pA2 values of 7.48 +/- 0.57 vs 7.43 +/- 0.58). Unexpectedly, the alpha 1-antagonist prazosin stimulated insulin secretion from islets of obese but not lean rats. Functional characteristics of the alpha-adrenoceptors on fa/fa islets are thus similar to those recently designated alpha 2B. Altered expression of alpha-adrenoceptors on pancreatic islets of fa/fa rats may contribute to changes in the pertussis toxin-independent pathway of epinephrine action previously observed.