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


ABSTRACT: Intracellular chloride concentration ([Cl-]i) in pancreatic ?-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 ?-cells, but particularly in insulin-secreting ?-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 ?-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 "neuron-specific" KCC2 co-transporter is expressed in pancreatic islet ?-cells where it modulates Ca2+-dependent insulin secretion.

SUBMITTER: Kursan S 

PROVIDER: S-EPMC5431760 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The neuronal K<sup>+</sup>Cl<sup>-</sup> co-transporter 2 (Slc12a5) modulates insulin secretion.

Kursan Shams S   McMillen Timothy S TS   Beesetty Pavani P   Dias-Junior Eduardo E   Almutairi Mohammed M MM   Sajib Abu A AA   Kozak J Ashot JA   Aguilar-Bryan Lydia L   Di Fulvio Mauricio M  

Scientific reports 20170511 1


Intracellular chloride concentration ([Cl<sup>-</sup>]<sub>i</sub>) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl<sup>-</sup> loaders such as the Na<sup>+</sup>K<sup>+</sup>2Cl<sup>-</sup> co-transporter 1 (Slc12a2) over Cl<sup>-</sup>extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" K<sup>+</sup>Cl<sup>-<  ...[more]

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