科研之友
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摘要
Pancreatic beta-cells express several ion channels of the transient receptor potential family, which play important roles in mediating the stimulus-secretion coupling. One of these channels, the TRPM4 is a Ca2+-activated monovalent cation channel. This channel is inhibited by 9-phenanthrol, which also inhibits the TMEM16a Cl- channel, and activates the Ca2+-activated K+ channel, K(ca)3.1. The net effects of ion-channel modulation by 9-phenantherol on the insulin secretion remain unclear. We tested the effects of 9-phenanthrol on glucose-and GLP-1-induced insulin secretion from isolated rat islets in static incubations. When applied to the islets in the presence of 3.3mM glucose, 9-phenanthrol caused a small increase in insulin secretion (similar to 7% of the insulin secretion stimulated by 10mM glucose). 10 mu M 9-phenanthrol did not inhibit glucose-or GLP-1-induced insulin secretion. 20 mu M and 30 mu M 9-phenanthrol inhibited glucose-induced insulin secretion by similar to 80% and similar to 85%, respectively. Inhibition of the GLP-1-induced insulin secretion by 20 mu M and 30 mu M 9-phenanthrol was 65% and 94%, respectively. Our study shows that the major effect of 9-phenanthrol on the islets is a strong inhibition of insulin secretion, and we speculate that compounds related to 9-phenanthrol may be potentially useful in treating the pancreatogenous hyperinsulinemic hypoglycemia syndromes.
- 出版日期2017
