Title: Correlation between GABA release from rat islet beta-cells and their metabolic state
Authors: Winnock, Frederic
Ling, Zhidong
De Proft, Rene
Dejonghe, Sandra
Schuit, Frans
Gorus, Frans
Pipeleers, Daniel # ×
Issue Date: Apr-2002
Series Title: American Journal of Physiology: Endocrinology and Metabolism vol:282 issue:4 pages:E937-E942
Abstract: Pancreatic beta-cells express glutamate decarboxylase (GAD), which is responsible for the production and release of gamma-aminobutyric acid (GABA). Over a 24-h culture period, total GABA release by purified rat beta-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/10(3) 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 beta-cell activities were inhibited by addition of diazoxide, verapamil, or cycloheximide or by reduction of extracellular calcium levels; it was counteracted when beta-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 beta-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 beta-cells, and hence GABA production and release, is compatible with previous findings on ATP suppression of brain GAD activity.
ISSN: 0193-1849
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
× corresponding author
# (joint) last author

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