Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release.
Glucagon, secreted from islet alpha-cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of beta-cell secretory products zinc and insulin on isolated rat alpha-cells, intact islets, and perfused pancreata. Islet glucagon secretion was markedly zinc sensitive (IC(50) = 2.7 micromol/l) more than insulin release (IC(50) = 10.7 micromol/l). Glucose, the mitochondrial substrate pyruvate, and the ATP-sensitive K(+) channel (K(ATP) channel) inhibitor tolbutamide stimulated isolated alpha-cell electrical activity and glucagon secretion. Zinc opened K(ATP) channels and inhibited both electrical activity and pyruvate (but not arginine)-stimulated glucagon secretion in alpha-cells. Insulin transiently increased K(ATP) channel activity, inhibited electrical activity and glucagon secretion in alpha-cells, and inhibited pancreatic glucagon output. Insulin receptor and K(ATP) channel subunit transcripts were more abundant in alpha- than beta-cells. Transcript for the glucagon-like peptide 1 (GLP-1) receptor was not detected in alpha-cells nor did GLP-1 stimulate alpha-cell glucagon release. beta-Cell secretory products zinc and insulin therefore inhibit glucagon secretion most probably by direct activation of K(ATP) channels, thereby masking an alpha-cell metabolism secretion coupling pathway similar to beta-cells.
Franklin
Isobel
I
Department of Cell PhysiologyMetabolism, University Medical Centre, 1211 Geneva 4, Switzerland.
Gromada
Jesper
J
Gjinovci
Asllan
A
Theander
Sten
S
Wollheim
Claes B
CB
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000502:physiology
D007328:Insulin; D015221:Potassium Channels; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005934:Glucagon; D015032:Zinc