Comparison of the effects of leucines, non-metabolizable leucine analogues and other insulin secretagogues on the activity of glutamate dehydrogenase.
Glutamate dehydrogenase (GLDH) from bovine liver was employed in 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 alpha-ketoisocaproic acid lacked significant effects on GLDH activity. Small and diverging effects were obtained with sulfonvlurea 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.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002271:Carbutamide / Q000494:pharmacology; D002417:Cattle; D004054:Diethylstilbestrol / Q000494:pharmacology; D005913:Glipizide / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014044:Tolbutamide / Q000494:pharmacology
D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007004:Hypoglycemic Agents; D004054:Diethylstilbestrol; D014044:Tolbutamide; D002271:Carbutamide; D005969:Glutamate Dehydrogenase; D007930:Leucine; D005913:Glipizide