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The KATP Channel and the Sulfonylurea Receptor

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Molecular Basis of Pancreas Development and Function

Part of the book series: Endocrine Updates ((ENDO,volume 11))

Abstract

ATP-sensitive K+ channels (KAgp channels) were first described in cardiac myocytes (1) and were subsequently found in many other tissues including pancreatic 13-cells (25), skeletal muscle (6), smooth muscle (7), brain (8), pituitary (9), and kidney (10) and in mitochondria (11). KA,p channels were originally characterized by inhibition when the ATP concentration at the cytoplasmic surface was increased (12). It is now known that regulation of KATP channel activity is complex, involving factors including nucleotide diphosphates such as ADP, Mgt*, and phosphatidylinositol bisphosphate (13-18). KATP channels play important roles in endocrine cells, muscles, and neurones, by coupling metabolic state to membrane potential (12,19,20). In pancreatic 13 cells, KATP channels regulate glucose-induced insulin secretion. Inhibition of the KATP channels by glucose depolarizes the 13-cell membrane, leading to opening of the voltage-dependent calcium channels (VDCCs), and allowing calcium influx. The rise in intracellular calcium concentration ([Ca21) in the 13-cell triggers exocytosis of the insulin granules. While the K+ channel opener diazoxide inhibits insulin secretion by activating the KATP channels, sulfonylureas such as glibenclamide, which is widely used in the treatment of type 2 diabetes mellitus, stimulate insulin release by inhibiting the KATP channels (21,22) Fig1 The cloning of members of the inwardly rectifying K+ channel subfamily Kir6.0 and the sulfonylurea receptors has clarified the structure of KA,p channels and revealed a new paradigm of channel/receptor assembly.

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  1. Chiba University, Chiba 260-8670, Japan

    Susumu Seino M.D., D.M.Sci., Takashi Miki M.D., Ph.D. & Hideki Yano M.D., D.M.Sci.

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  1. Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA

    Joel F. Habener M.D.

  2. Department of Medicine, Clinical and Molecular Endocrinology, New York University Medical Center, New York, NY

    Mehboob A. Hussain M.D.

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Seino, S., Miki, T., Yano, H. (2001). The KATP Channel and the Sulfonylurea Receptor. In: Habener, J.F., Hussain, M.A. (eds) Molecular Basis of Pancreas Development and Function. Endocrine Updates, vol 11. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1669-9_6

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  • DOI: https://doi.org/10.1007/978-1-4615-1669-9_6

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5669-1

  • Online ISBN: 978-1-4615-1669-9

  • eBook Packages: Springer Book Archive

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