Molecular Pharmacology, Vol 11, 759-765, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Insulin Biosynthesis by Alloxan, Streptozotocin, and N-Nitrosomethylurea

¹ Department of Histology, University of Uppsala, Uppsala, Sweden

Isolated mouse pancreatic islets were used to evaluate the effect of a single intravenous injection of alloxan (100 mg/kg body weight), streptozotocin (200 mg/kg), or N-nitrosomethylurea (78 mg/kg) on glucose-stimulated biosynthesis of insulin in the B-cell. The animals were killed 10 min after injection of the drugs, and the rate of insulin synthesis was estimated by measurements of the incorporation of [³H]leucine into proinsulin and insulin. Alloxan completely blocked insulin biosynthesis, whereas with streptozotocin and N-nitrosomethylurea the inhibition was only partial. Nicotinamide restored insulin biosynthesis after the latter drugs but was completely without effect on alloxan-induced inhibition.

Note:
ACKNOWLEDGMENTS The author is indebted to Associate Professor Claes Hellerström for valuable advice and review of the manuscript. The skillful technical assistance of Mrs. Parri Wentzel is gratefully acknowledged.