Kalaiselvan Krishnan1, Zuheng Ma, Anneli Björklund, Md Shahidul Islam. 1. From the *Department of Clinical Science and Education, Karolinska Institutet, South Hospital, Stockholm, Sweden; †Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; and ‡Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden.
Abstract
OBJECTIVE: Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca(2+)-activated monovalent cation channel, is involved in the stimulus-secretion coupling in the mouse pancreatic β-cells. We have studied the role of the TRPM5 channel in regulating insulin secretion and cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) in the rat β-cells by using triphenylphosphine oxide, a selective inhibitor of the channel. METHODS: Insulin secretion from islets from Sprague-Dawley rats was measured in batch incubations. Cytoplasmic free Ca(2+) concentration was measured from single β-cells by fura-2-based microfluorometry. RESULTS: Triphenylphosphine oxide did not alter insulin secretion and [Ca(2+)](i) response triggered by KCl or fructose. It inhibited insulin secretion in response to glucose, L-arginine, and glucagon-like peptide 1. It also inhibited glucose-induced insulin secretion by mechanisms that are independent of the adenosine triphosphate-sensitive potassium channels and [Ca(2+)](i) increase. CONCLUSIONS: Our results suggest that in the rat islets, TRPM5 is involved in mediating insulin secretion by glucose and l-arginine and in potentiating the glucose-induced insulin secretion by glucagon-like peptide 1.
OBJECTIVE: Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca(2+)-activated monovalent cation channel, is involved in the stimulus-secretion coupling in the mouse pancreatic β-cells. We have studied the role of the TRPM5 channel in regulating insulin secretion and cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) in the rat β-cells by using triphenylphosphine oxide, a selective inhibitor of the channel. METHODS:Insulin secretion from islets from Sprague-Dawley rats was measured in batch incubations. Cytoplasmic free Ca(2+) concentration was measured from single β-cells by fura-2-based microfluorometry. RESULTS:Triphenylphosphine oxide did not alter insulin secretion and [Ca(2+)](i) response triggered by KCl or fructose. It inhibited insulin secretion in response to glucose, L-arginine, and glucagon-like peptide 1. It also inhibited glucose-induced insulin secretion by mechanisms that are independent of the adenosine triphosphate-sensitive potassium channels and [Ca(2+)](i) increase. CONCLUSIONS: Our results suggest that in the rat islets, TRPM5 is involved in mediating insulin secretion by glucose and l-arginine and in potentiating the glucose-induced insulin secretion by glucagon-like peptide 1.
Authors: Abdelilah Arredouani; Margarida Ruas; Stephan C Collins; Raman Parkesh; Frederick Clough; Toby Pillinger; George Coltart; Katja Rietdorf; Andrew Royle; Paul Johnson; Matthias Braun; Quan Zhang; William Sones; Kenju Shimomura; Anthony J Morgan; Alexander M Lewis; Kai-Ting Chuang; Ruth Tunn; Joaquin Gadea; Lydia Teboul; Paula M Heister; Patricia W Tynan; Elisa A Bellomo; Guy A Rutter; Patrik Rorsman; Grant C Churchill; John Parrington; Antony Galione Journal: J Biol Chem Date: 2015-07-07 Impact factor: 5.157