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Journal of Diabetes Research
Volume 2017, Article ID 5131785, 5 pages
Research Article

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

1Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
2Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Research Center, 3rd Floor, 118 83 Stockholm, Sweden
3Department of Emergency Care and Internal Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

Correspondence should be addressed to Md. Shahidul Islam; es.ik@malsi.ludihahs

Received 26 May 2017; Revised 18 August 2017; Accepted 10 September 2017; Published 2 October 2017

Academic Editor: Craig S. Nunemaker

Copyright © 2017 Zuheng Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 compounds related to 9-phenanthrol may be potentially useful in treating the pancreatogenous hyperinsulinemic hypoglycemia syndromes.