A TRPM4 Inhibitor 9-Phenanthrol Inhibits Glucose- and Glucagon-Like Peptide 1-Induced Insulin Secretion from Rat Islets of Langerhans

Journal of Diabetes Research
Zuheng MaMd Shahidul Islam

Abstract

Pancreatic β-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, Kca3.1. 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 3.3 mM glucose, 9-phenanthrol caused a small increase in insulin secretion (~7% of the insulin secretion stimulated by 10 mM glucose). 10 μM 9-phenanthrol did not inhibit glucose- or GLP-1-induced insulin secretion. 20 μM and 30 μM 9-phenanthrol inhibited glucose-induced insulin secretion by ~80% and ~85%, respectively. Inhibition of the GLP-1-induced insulin secretion by 20 μM and 30 μM 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 compou...Continue Reading

References

Jun 30, 2006·Cell Calcium·Henrique ChengReinhold Penner
Feb 26, 2008·British Journal of Pharmacology·T GrandR Guinamard
Feb 4, 2011·Advances in Experimental Medicine and Biology·Md Shahidul Islam
Jan 18, 2014·British Journal of Pharmacology·R GuinamardC A Del Negro
Jan 13, 2015·British Journal of Pharmacology·Sarah K BurrisJonathan H Jaggar
Nov 17, 2015·The Journal of Clinical Investigation·Makoto ShigetoPatrik Rorsman
Nov 20, 2015·Pflügers Archiv : European journal of physiology·Raphaël CrutzenPhilippe E Golstein

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Citations

Aug 3, 2021·Frontiers in Pharmacology·Prakash ArullampalamHugues Abriel

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