Dopamine (DA) has a vital role in the central nervous system and also modulates lipid and glucose metabolism. The present study aimed to investigate the effect of dopamine on insulin secretion and the underlying mechanisms in rat pancreatic β-cells. Data from the radioimmunoassay indicated that dopamine inhibited insulin secretion in a glucoseand dose-dependent manner. This inhibitory effect of dopamine was mediated mainly by D2-like receptors, but not D1-like receptors. Whole-cell patch-clamp recordings showed that dopamine decreased voltage-dependent Ca 2+ channel currents, which could be reversed by inhibition of the D2-like receptor. Dopamine increased voltage-dependent potassium (K V) channel currents and shortened action potential duration, which was antagonized by inhibition of D2-like receptors. Further experiments showed that D2-like receptor activation by quinpirole increased K V channel currents. In addition, using calcium imaging techniques, we found that dopamine reduced intracellular Ca 2+ concentration, which was also reversed by D2-like receptor antagonists. Similarly, quinpirole was found to decrease intracellular Ca 2+ levels. Taken together, these findings demonstrate that dopamine inhibits insulin secretion mainly by acting on D2-like receptors, inhibiting Ca 2+ channels, and activating Kv channels. This process results in shortened action potential duration and decreased intracellular Ca 2+ levels in β-cells. This work offers new insights into a glucose-dependent mechanism whereby dopamine regulates insulin secretion.
Insulin secretion is essential for maintenance of glucose homeostasis. An important intracellular signal regulating insulin secretion is cAMP. In this report, we showed that an increase of cAMP induced by adenylyl cyclase (AC) activator forskolin or by cAMP analog db-cAMP not only potentiated insulin secretion but also inhibited Kv channels, and these effects were reversed by AC inhibitor SQ22536. The cAMP-mediated Kv channel inhibition resulted in prolongation of action potential duration, which partly accounts for the elevation of intracellular Ca 2C induced by activation of cAMP signaling. Taken together, the results suggest that Kv channels are involved in cAMP-potentiated insulin secretion in pancreatic b cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.