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Sci Rep. 2017 May 11;7(1):1732. doi: 10.1038/s41598-017-01814-0.

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

Author information

1
Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH, 45435, USA.
2
Pacific Northwest Diabetes Research Institute, Seattle, WA, 98122, USA.
3
Department of Neuroscience, Cell Biology and Physiology, Wright State University, School of Medicine, Dayton, OH, 45435, USA.
4
Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
5
Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH, 45435, USA. Mauricio.DiFulvio@wright.edu.

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 "neuron-specific" KCC2 co-transporter is expressed in pancreatic islet β-cells where it modulates Ca2+-dependent insulin secretion.

PMID:
28496181
PMCID:
PMC5431760
DOI:
10.1038/s41598-017-01814-0
[Indexed for MEDLINE]
Free PMC Article

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