The two pore channel TPC2 is dispensable in pancreatic β-cells for normal Ca²⁺ dynamics and insulin secretion

Cell Calcium
Matthew C CaneGuy A Rutter

Abstract

Ca(2+) signals are central to the stimulation of insulin secretion from pancreatic β-cells by glucose and other agents, including glucagon-like peptide-1 (GLP-1). Whilst Ca(2+) influx through voltage-gated Ca(2+) channels on the plasma membrane is a key trigger for glucose-stimulated secretion, mobilisation of Ca(2+) from acidic stores has been implicated in the control of more localised Ca(2+) changes and membrane potential. Nicotinic acid adenine dinucleotide phosphate (NAADP), generated in β-cells in response to high glucose, is a potent mobiliser of these stores, and has been proposed to act through two pore channels (TPC1 and TPC2, murine gene names Tpcn1 and Tpcn2). Whilst the role of TPC1 in the control of Ca(2+) mobilisation and insulin secretion was recently confirmed, conflicting data exist for TPC2. Here, we used the selective and efficient deleter strain, Ins1Cre to achieve β-cell selective deletion of the Tpcn2 gene in mice. βTpcn2 KO mice displayed normal intraperitoneal and oral glucose tolerance, and glucose-stimulated Ca(2+) dynamics and insulin secretion from islets were similarly normal. GLP-1-induced Ca(2+) increases involved an increase in oscillation frequency from 4.35 to 4.84 per minute (p=0.04) at 8mM g...Continue Reading

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Citations

Jul 22, 2016·Channels·Sandra Feijóo-BandínFrancisca Lago
Jan 18, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Makoto ShigetoKohei Kaku
May 4, 2017·Diabetes, Obesity & Metabolism·Guy A RutterIsabelle Leclerc
Feb 23, 2020·Seminars in Cell & Developmental Biology·Olof Idevall-Hagren, Anders Tengholm
May 23, 2021·Scientific Reports·Paula Maria HeisterAntony Galione

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Methods Mentioned

BETA
gene trap
PCR
fluorescence microscopy

Software Mentioned

[UNK]
GraphPad PRISM

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