Correlation between GABA release from rat islet β-cells and their metabolic state

Author:

Winnock Frederic1,Ling Zhidong1,De Proft Rene1,Dejonghe Sandra1,Schuit Frans1,Gorus Frans1,Pipeleers Daniel1

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

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