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Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37)

Nature volume 361, pages 362–365 (1993)Cite this article

Abstract

NON-INSULIN-DEPENDENT diabetes mellitus (NIDDM, type 2 diabetes) is a disorder of glucose homeostasis characterized by hyperglycaemia, peripheral insulin resistance, impaired hepatic glucose metabolism, and diminished glucose-dependent secretion of insulin from pancreatic β-cells1. Glucagon-like-peptide-1(7-37) (GLP-1)2 is an intestinally derived hormone that may be useful for the treatment of NIDDM because it acts in vivo to increase the level of circulating insulin, and thus lower the concentration of blood glucose3,4. This therapeutic effect may result from the ability of GLP-1 to compensate for a defect in the glucose signalling pathway that regulates insulin secretion from β-cells. In support of this concept we report here that GLP-1 confers glucose sensitivity to glucose-resistant p-cells, a phenomenon we term glucose competence. Induction of glucose competence by GLP-1 results from its synergistic interaction with glucose to inhibit metabolically regulated potassium channels that are also targeted for inhibition by sulphonylurea drugs commonly used in the treatment of NIDDM5. Glucose competence allows membrane depolarization, the generation of action potentials, and Ca2+ influx, events that are known to trigger insulin secretion6,7.

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Author notes

  1. Willem M. Kiihtreiber

    Present address: BioHybrid Technologies Inc., 910 Turnpike Road, Shrewsbury, Massachusetts, 01545, USA

Authors and Affiliations

  1. Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02114, USA

    George G. Holz IV IV & Joel F. Habener

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  1. George G. Holz IV IV
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  3. Joel F. Habener
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Holz IV, G., Kiihtreiber, W. & Habener, J. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37). Nature 361, 362–365 (1993). https://doi.org/10.1038/361362a0

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