Affiliation:
1. Diabetes Research Center, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
Abstract
Pancreatic β-cells express glutamate decarboxylase (GAD), which is responsible for the production and release of γ-aminobutyric acid (GABA). Over a 24-h culture period, total GABA release by purified rat β-cells is eightfold higher than the cellular GABA content and can thus be used as an index of cellular GAD activity. GABA release is 40% reduced by glucose (58 pmol/103 cells at 10 mM glucose vs. 94 pmol at 3 mM glucose, P < 0.05). This suppressive effect of glucose was not observed when glucose metabolism was blocked by mannoheptulose or 2,4-dinitrophenol; it was amplified when ATP-dependent β-cell activities were inhibited by addition of diazoxide, verapamil, or cycloheximide or by reduction of extracellular calcium levels; it was counteracted when β-cell functions were activated by nonmetabolized agents, such as glibenclamide, IBMX, glucagon, or glucacon-like peptide-1 (GLP-1), which are known to stimulate calcium-dependent activities, such as hormone release and calcium-dependent ATPases. These observations suggest that GABA release from β-cells varies with the balance between ATP-producing and ATP-consuming activities in the cells. Less GABA is released in conditions of elevated glucose metabolism, and hence ATP production, but this effect is counteracted by ATP-dependent activities. The notion that increased cytoplasmic ATP levels can suppress GAD activity in β-cells, and hence GABA production and release, is compatible with previous findings on ATP suppression of brain GAD activity.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism
Cited by
50 articles.
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