Correction: Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet.

[This corrects the article DOI: 10.1371/journal.pone.

Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet.

Cystic fibrosis (CF) is due to mutations in the CF-transmembrane conductance regulator (CFTR) and CF-related diabetes (CFRD) is its most common co-morbidity, affecting ~50% of all CF patients, significantly influencing pulmonary function and longevity. Yet, the complex pathogenesis of CFRD remains unclear. Two non-mutually exclusive underlying mechanisms have been proposed in CFRD: i) damage of the endocrine cells secondary to the severe exocrine pancreatic pathology and ii) intrinsic β-cell impairment of the secretory response in combination with other factors.

Impaired glucose tolerance, glucagon, and insulin responses in mice lacking the loop diuretic-sensitive transporter.

The NaK2Cl cotransporter-2 (, ) is abundantly expressed in the kidney and its inhibition with the loop-diuretics bumetanide and furosemide has been linked to transient or permanent hyperglycemia in mice and humans. Notably, is expressed at low levels in hypothalamic neurons and in insulin-secreting β-cells of the endocrine pancreas. The present study was designed to determine if global elimination of one of the products, i.

The neuronal KCl co-transporter 2 (Slc12a5) modulates insulin secretion.

Intracellular chloride concentration ([Cl]) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl loaders such as the NaK2Cl co-transporter 1 (Slc12a2) over Clextruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" KCl 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).

Plasma Membrane Targeting of Endogenous NKCC2 in COS7 Cells Bypasses Functional Golgi Cisternae and Complex N-Glycosylation.

NaK2Cl co-transporters (NKCCs) effect the electroneutral movement of Na-K and 2Cl ions across the plasma membrane of vertebrate cells. There are two known NKCC isoforms, NKCC1 () and NKCC2 (). NKCC1 is a ubiquitously expressed transporter involved in cell volume regulation, Cl homeostasis and epithelial salt secretion, whereas NKCC2 is abundantly expressed in kidney epithelial cells of the thick ascending loop of Henle, where it plays key roles in NaCl reabsorption and electrolyte homeostasis.

A highly efficient strategy to determine genotypes of genetically-engineered mice using genomic DNA purified from hair roots.

Genotyping of genetically-engineered mice is necessary for the effective design of breeding strategies and identification of mutant mice. This process relies on the identification of DNA markers introduced into genomic sequences of mice, a task usually performed using the polymerase chain reaction (PCR). Clearly, the limiting step in genotyping is isolating pure genomic DNA.

Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice.

The products of the Slc12a1 and Slc12a2 genes, commonly known as Na(+)-dependent K(+)2Cl(-) co-transporters NKCC2 and NKCC1, respectively, are the targets for the diuretic bumetanide. NKCCs are implicated in the regulation of intracellular chloride concentration ([Cl(-)]i) in pancreatic β-cells, and as such, they may play a role in glucose-stimulated plasma membrane depolarization and insulin secretion. Unexpectedly, permanent elimination of NKCC1 does not preclude insulin secretion, an event potentially linked to the homeostatic regulation of additional Cl(-) transporters expressed in β-cells.