Glucose-sensing mechanisms in pancreatic beta-cells.
The appropriate secretion of insulin from pancreatic beta-cells is critically important to the maintenance of energy homeostasis. The beta-cells must sense and respond suitably to postprandial increases of blood glucose, and perturbation of glucose-sensing in these cells can lead to hypoglycaemia or hyperglycaemias and ultimately diabetes. Here, we review beta-cell glucose-sensing with a particular focus on the regulation of cellular excitability and exocytosis. We examine in turn: (i) the generation of metabolic signalling molecules; (ii) the regulation of beta-cell membrane potential; and (iii) insulin granule dynamics and exocytosis. We further discuss the role of well known and putative candidate metabolic signals as regulators of insulin secretion.
MacDonald
Patrick E
PE
Duke University Medical Center Sarah W. Stedman Nutrition and Metabolism Center Durham, NC 27704, USA. pmacdonald@bcell.org
Joseph
Jamie W
JW
Rorsman
Patrik
P
D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D015220:Calcium Channels / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D000214:Acyl Coenzyme A; D015220:Calcium Channels; D007328:Insulin; D015221:Potassium Channels; D009249:NADP; D000255:Adenosine Triphosphate; D005947:Glucose