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1 Units of Pathology,
1 Nephrology,
2 Endocrinology and Metabolism, Faculty of Medicine, Université Catholique de Louvain, Avenue Hippocrate, B-1200 Brussels, Belgium
(Requests for offprints should be addressed to J C Henquin; Email: henquin{at}endo.ucl.ac.be)
Na+/H+ exchangers (NHE) constitute a family of membrane antiporters that contribute to the regulation of cellular pH and volume in many tissues, including pancreatic islets. We investigated the molecular identity of NHE in rodent and human endocrine pancreas, and determined its cellular and subcellular localization. NHE1 was the most abundantly expressed isoform in rat islets, and was also expressed in mouse and human islets. By western blot, an antiserum raised against the C-terminus end of NHE1 confirmed the presence of a ~100 kDa protein corresponding to NHE1 in islets and unexpectedly unveiled the existence of a ~65 kDa cross-reactive NHE1-related protein. By immunohistochemistry, the antiserum labelled the membranes of pancreatic acini and ducts, but also diffusely stained the cytoplasm of insulin, glucagon and somatostatin cells as well as endocrine cells of the adrenal medulla. Electron microscopy localized the NHE1 immunoreactivity in the membrane of secretory granules, an unexpected finding supported by a decrease in immunohistochemical signal in degranulated ß-cells. Islets of Slc9A1swe/swe mice, which lack full NHE1 protein, were found to express an mRNA corresponding to the 3' end of NHE1 as well as the ~65 kDa protein. They still showed the cytoplasmic labelling but no plasma membrane was stained. We conclude that both the full-length and the shorter-splice variant of NHE1 are expressed in all cell types of the endocrine pancreas and in the adrenal medulla of rodents and humans. The complete protein is addressed to the plasma membrane and the shorter one to the membrane of secretory granules where its function remains to be established.
This article has been cited by other articles:
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P. Stiernet, M. Nenquin, P. Moulin, J.-C. Jonas, and J.-C. Henquin Glucose-induced Cytosolic pH Changes in beta-Cells and Insulin Secretion Are Not Causally Related: STUDIES IN ISLETS LACKING THE NA+/H+ EXCHANGER NHE1 J. Biol. Chem., August 24, 2007; 282(34): 24538 - 24546. [Abstract] [Full Text] [PDF] |
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