Summary
Glutamate dehydrogenase (GLDH) from bovine liver was employed in a model system for testing a possible role of GLDH in insulin release. The ability of different insulin secretagogues to stimulate the activity of the diethylstilbestrol-inhibited enzyme was tested. The two insulin-releasing amino acids, L-leucine and its non-metabolizable analogue 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid [b(−)-BCH], were the best stimulators of GLDH activity. The non-secreting stereoisomers, D-leucine and b(+)-BCH, were less effective. Glucose, L-arginine and the leucine metabolite α-ketoisocaproic acid lacked significant effects on GLDH activity. Small and diverging effects were obtained with sulfonylurea compounds: whereas carbutamide caused slight stimulation, tolbutamide and glipizide had no effect, and glibenclamide was an inhibitor. The specificity of the insulin-releasing amino acids L-leucine and b(−)-BCH in stimulating GLDH activity makes it tempting to speculate about a connection between allosteric regulation of pyridine nucleotide-dependent enzymes and insulin release.
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Gylfe, E. Comparison of the effects of leucines, non-metabolizable leucine analogues and other insulin secretagogues on the activity of glutamate dehydrogenase. Acta diabet. lat 13, 20–24 (1976). https://doi.org/10.1007/BF02591577
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DOI: https://doi.org/10.1007/BF02591577