Potentiation of the hypoglycemic effect of insulin by thiorphan, an enkephalinase inhibitor |
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Authors: | R E Chipkin W Kreutner W Billard |
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Affiliation: | 1. INSERM U. 55, CNRS ERA 494, Hopital St Antoine, 184 rue de Fg St Antoine, 75571 Paris Cédex 12, France;1. Lab. Roussel-Uclaf, 102 route de Noisy, 93230 Romainville, France |
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Abstract: | 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. |
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Keywords: | To whom all correspondence should be addressed. |
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