Potentiation of the hypoglycemic effect of insulin by thiorphan, an enkephalinase inhibitor.
Insulin administration to rats produced a dose-related hypoglycemia. When insulin and the enkephalinase (Enk'ase) inhibitor thiorphan (30 or 100 mg/kg s.c.) were co-administered, there was a potentiation of the hypoglycemic response to insulin; these doses of thiorphan alone had no significant effect on plasma glucose. When tested in vitro against isolated Enk'ase, both insulin and its beta-chain inhibited the catabolism of [Met5]enkephalin. Theoretically, thiorphan blocked the catabolism of insulin by inhibiting Enk'ase. Alternatively, thiorphan acted as an inhibitor of another insulin-catabolizing enzyme having similar substrate requirements as Enk'ase.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D004357:Drug Synergism; D004744:Enkephalin, Methionine / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D015260:Neprilysin; D011480:Protease Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D001786:Blood Glucose; D007328:Insulin; D011480:Protease Inhibitors; D004744:Enkephalin, Methionine; D015244:Thiorphan; D008625:Tiopronin; D015260:Neprilysin