Role of Na/H exchange in insulin secretion by islet cells.
OBJECTIVE
Sodium/hydrogen exchangers (NHEs) are a large family of transport proteins catalyzing the exchange of cations for protons across lipid bilayer membranes. Several isoforms are expressed in β cells of the endocrine pancreas, including the recently discovered and poorly characterized isoform NHA2. This review will summarize advances in our understanding of the roles of NHEs in the regulation of insulin secretion in β cells.


RESULTS
Plasmalemmal full-length NHE1 defends β cells from intracellular acidification, but has no role in stimulus-secretion coupling and is not causally involved in glucose-induced alkalinization of the β cell. The function of a shorter NHE1 splice variant, which localizes to insulin-containing large dense core vesicles, remains currently unknown. In contrast, in-vitro and in-vivo studies indicate that the NHA2 isoform is required for insulin secretion and clathrin-mediated endocytosis in β cells.


CONCLUSIONS
Recent data highlight the importance of NHEs in the regulation of cellular pH, clathrin-mediated endocytosis and insulin secretion in β cells. Based on these studies, a pathophysiological role of NHEs in human disorders of the endocrine pancreas seems likely and should be investigated.
Division of Nephrology, Hypertension and Clinical Pharmacology, University Hospital of Bern, and Institute of Biochemistry, Molecular Medicine and NCCR TransCure, University of Bern, Bern, Switzerland.
Christine
C
Deisl
Giuseppe
G
Albano
Daniel G
DG
Fuster
D017920:Antiporters / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D017920:Antiporters; D027682:Cation Transport Proteins; D007328:Insulin; C490998:SLC9A1 protein, human; C527589:SLC9B2 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers