Studies on the ability of compounds to block the diabetogenic activity of streptozotocin.

Abstract

Evidence is presented that the early hyperglycemia (two to four hours after injection) following streptozotocin administration is not a result of an interference with insulin action, since streptozotocin did not block insulin action on skeletal muscle in vitro. Compounds with known metabolic effects were tested for their ability to block streptozotocin-induced diabetes. Mannoheptulose, glucosamine, diazoxide, NAD, glucose, epinephrine, 3,5-dimethylpyrazole, 3-carboxy-5-methylpyrazole, glutamic acid, glycine, asparagine, cysteine, sodium tolbutamide, guanidoacetic acid, glutathione, p-aminobenzoic acid, and ethyl alcohol were ineffective as blocking agents. Pretreatment with pyrazinamid blocked streptozotocin diabetes,but was ineffective following streptozotocin treatment. 2-carboxypyrazine (the metabolite of pyrazinamide) did not block streptozotocin diabetogenic activity. Administration of 2-deoxyglucose blocked streptozotocin-induced diabetes; this is postulated to be the result of an interference with streptozotocin transport into the β cell. Pretreatment with nicotinamide, or treatment as long as two hours after streptozotocin, blocked the diabetogenic effect of streptozotocin. Nicotinic acid was ineffective. It is postulated that streptozotocin interferes with NAD formation in the β cell, and that nicotinamide treatment abolishes the streptozotocin effect by its ability to maintain ah adequate concentration of NAD in the β cell.