The pancreatic beta-cell as a fuel sensor: an electrophysiologist's viewpoint.
The pancreatic beta cell serves as the fuel sensor of the entire body and controls, via secretion of the hypoglycaemic hormone insulin, the blood glucose concentrations within narrow limits by regulation of glucose uptake and release. During the last 30 years, a combination of biochemical and ultrastructural approaches has resulted in dramatic progress in the understanding of the processes by which glucose and other nutrients modulate the release of insulin. The beta cells have also been investigated using electrophysiological techniques and were thus found to be electrically excitable and to undergo complex changes in their membrane potential when exposed to glucose and other stimulators of secretion. The application of the patch-clamp technique to the pancreatic islet preparations has revolutionized the understanding of how bioelectrical processes participate in the fuel-sensing of the beta cell. An important achievement was the identification of an ATP-sensitive K(+)-channel as the resting and glucose-sensitive membrane conductance of the beta cell. This channel also constitutes the target of the hypoglycaemic sulphonylureas: a group of compounds which have been used successfully in the treatment of insulin-dependent diabetes mellitus for several decades.
Rorsman
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Department of Islet Cell Physiology, Novo Nordisk A/S, Copenhagen, Denmark.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004594:Electrophysiology; D005089:Exocytosis; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D008954:Models, Biological; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D005947:Glucose; D002118:Calcium