Trends in Endocrinology & Metabolism
ReviewPotassium Channels, Sulphonylurea Receptors and Control of Insulin Release
Section snippets
K+ Channels and Sulphonylurea Receptors
Insulin-secreting cells express a KATP channel complex formed by the interaction of subunits belonging to at least two distinct families of proteins (for a review see Ref. 2) (Fig. 2). The K+-selective pore or tunnel is formed by the Kir6.2 subunit, a member of the inward rectifier K+ channel family. Kir6.2 shares ∼70% homology with Kir6.1, consists of 390 amino acids, and has a predicted membrane topology with two α-helical transmembrane domains linked by a highly conserved sequence of amino
K+ Channels and Unregulated Insulin Secretion
Hypoglycaemia is a relatively common childhood metabolic abnormality and when persistent or recurrent is most frequently a consequence of hyperinsulinism; neonatal hyperinsulinism (OMIM: 256450) (for a recent review see Ref. 18). Until recently, the pathophysiology of this group of conditions was not understood, although a defect in β-cell function was first suggested in 1981, when it was shown that glucose failed to promote a concentration-dependent release of insulin in tissue isolated from a
Future Directions
Progress in the areas covered in this review has been impressive over the past few years, yet many key questions remain. Are there additional KATP channel subunits to be discovered? How do nucleotides bring about opening and closure of channels after interactions with the subunits? How are the subunits associated and targeted to the cell membrane? The genetics of PHHI are still far from resolved; autosomal recessive and dominant inheritance have been described, as well as loss of maternal
Acknowledgements
Work in our laboratories is supported by the British Diabetic Association (MJD), the Medical Research Council (MJD) and the Economic Union (MJD, CÄ); and by Stiftelsen Clas Groschinskys minnesfond, Tore Nilssons Stiftelse, Åke Wibergs Stiftelse, Wilhelm och Martina Lundgrens vetenskapsfond, Swedish Medical Research Council (CÄ). KEC was supported by a Medical Research Council Studentship.
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