The long-term effects of subdiabetogenic doses of alloxan monohydrate (<70 mg/kg) were studied in the mouse. When injected intravenously at 50 and 60 mg/kg, alloxan induced a marked albeit transient hyperglycemia; plasma levels gradually declined after 15 d and were normal after 60 d in 20 of 31 animals. After injection of alloxan at the dose of 40 mg/kg, only a slight transient hyperglycemia was seen during the first 15 d. At 2 mo after alloxan injection, however, glucose- and carbachol-stimulated insulin secretion were markedly impaired in all animals treated with alloxan, including those with normoglycemia. The pancreatic content of insulin was significantly reduced at 2 mo after treatment of alloxan at 50 or 60 mg/kg, but, however, not after 40 mg/kg. It is concluded that (1) Subdiabetogenic doses of alloxan (50 and 60 mg/kg) induce a persistent hyperglycemia only in approx 25 of the animals; (2) The insulin secretory responses to glucose and carbachol are impaired after alloxan treatment; and (3) Alloxan-induced B-cell toxicity is evident also in animals not developing permanent diabetes. Hence, although a repair process may be initiated after alloxan to normalize the hyperglycemia, insulin secretion and pancreatic insulin content do not normalize.
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