Long-term effects of alloxan in mice.
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.
Ahrén
B
B
Department of Medicine, Lund University, Malmö, Sweden.
Sundkvist
G
G
D000496:Alloxan / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D000496:Alloxan; D002217:Carbachol; D005947:Glucose