Evidence for endogenous urotensin-II as an inhibitor of insulin secretion: Study in the perfused rat pancreas

In the perfused rat pancreas, infusion of urotensin-II (UII), a somatostatin-like peptide, inhibits glucose-induced insulin secretion. We have resorted to specific antagonists of the UII receptor (UT), palosuran and urantide, to investigate whether endogenous UII also behaves as an inhibitor of beta-cell secretion. The insulinostatic effect of UII was counteracted by palosuran and by urantide but not by a somatostatin-receptor antagonist (cyclo-somatostatin). Furthermore, the insulinostatic effect of somatostatin was not reversed by palosuran. These results suggest that UII and somatostatin blocked beta-cell secretion via distinct receptors. Finally, in the absence of exogenous UII, both palosuran and urantide potentiated glucose-induced insulin release, thus supporting the concept that endogenous UII is an insulinostatic peptide. By virtue of their insulinotropic effect, UT antagonists may be considered potential drugs for treating the impaired insulin secretion characteristic of type 2 diabetic patients.