The neuronal K+ Cl- co-transporter 2 (Slc12a5) modulates insulin secretion

Scientific Reports
Shams KursanMauricio Di Fulvio

Abstract

Intracellular chloride concentration ([Cl-]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl- loaders such as the Na+K+2Cl- co-transporter 1 (Slc12a2) over Cl-extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" K+Cl- co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response. Three KCC2 splice variants were identified: the formerly described KCC2a and KCC2b along with a novel one lacking exon 25 (KCC2a-S25). This new variant is undetectable in brain or spinal cord, the only and most abundant known sources of KCC2. Inhibition of KCC2 activity in clonal MIN6 β-cells increases basal and glucose-stimulated insulin secretion and Ca2+ uptake in the presence of glibenclamide, an inhibitor of the ATP-dependent potassium (KATP)-channels, thus suggesting a possible mechanism underlying KCC2-dependent insulin release. We propose that the long-time considered ...Continue Reading

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Citations

Dec 12, 2017·Acta Physiologica·A D GreenP R Flatt
Nov 8, 2019·Biochemical Society Transactions·Mauricio Di Fulvio, Lydia Aguilar-Bryan
Oct 27, 2017·American Journal of Physiology. Endocrinology and Metabolism·Ivan Torre-VillalvazoGerardo Gamba
Nov 17, 2017·Molecular Membrane Biology·Bor Luen Tang
Aug 1, 2019·American Journal of Physiology. Cell Physiology·Lisa KellyMauricio Di Fulvio
Dec 3, 2020·PloS One·Mauricio Di FulvioLydia Aguilar-Bryan

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BETA
KJ535321
AF087436

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reverse transcription PCR
PCR
ELISA
Fluorescence
Profiler

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InCyt Im2
Geneious Suite
ImageJ
RGB Profiler
Origin

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