The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion
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,...
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Nature Portfolio
2017
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oai:doaj.org-article:d1c00f15f43e41669bcde19b13071f672021-12-02T11:41:20ZThe neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion10.1038/s41598-017-01814-02045-2322https://doaj.org/article/d1c00f15f43e41669bcde19b13071f672017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01814-0https://doaj.org/toc/2045-2322Abstract 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.Shams KursanTimothy S. McMillenPavani BeesettyEduardo Dias-JuniorMohammed M. AlmutairiAbu A. SajibJ. Ashot KozakLydia Aguilar-BryanMauricio Di FulvioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Shams Kursan Timothy S. McMillen Pavani Beesetty Eduardo Dias-Junior Mohammed M. Almutairi Abu A. Sajib J. Ashot Kozak Lydia Aguilar-Bryan Mauricio Di Fulvio The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| description |
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. |
| format |
article |
| author |
Shams Kursan Timothy S. McMillen Pavani Beesetty Eduardo Dias-Junior Mohammed M. Almutairi Abu A. Sajib J. Ashot Kozak Lydia Aguilar-Bryan Mauricio Di Fulvio |
| author_facet |
Shams Kursan Timothy S. McMillen Pavani Beesetty Eduardo Dias-Junior Mohammed M. Almutairi Abu A. Sajib J. Ashot Kozak Lydia Aguilar-Bryan Mauricio Di Fulvio |
| author_sort |
Shams Kursan |
| title |
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| title_short |
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| title_full |
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| title_fullStr |
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| title_full_unstemmed |
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion |
| title_sort |
neuronal k+cl− co-transporter 2 (slc12a5) modulates insulin secretion |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/d1c00f15f43e41669bcde19b13071f67 |
| work_keys_str_mv |
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