Abnormal B-cell function in neonatally streptozotocin-diabetic rats: insensitivity to alloxan toxicity.
The apparent toxicity of alloxan was compared in nondiabetic rats and rats made diabetic by injection with streptozotocin during neonatal life (STZ). In the perfused pancreas of nondiabetic rats, 1 mM alloxan rapidly but evanescently stimulated insulin secretion; this effect was followed by pronounced inhibition of the insulin response to 27 mM glucose (94% inhibition) or 1 mM 3-isobutyl-1-methylxanthine (76% inhibition). Conversely, in STZ-diabetic rats the stimulatory effect of alloxan was reduced to 22% of that elicited in nondiabetic rats. In further contrast, the inhibitory effect of alloxan exposure was abolished with regard to subsequent glucose-induced insulin secretion and attenuated with regard to 3-isobutyl-1-methylxanthine-induced insulin secretion. A relative insensitivity to alloxan was also seen in collagenase-isolated islets, where alloxan completely abolished glucose-induced insulin secretion in islets from nondiabetic rats, but only nonsignificantly reduced secretion (by 37%) in islets from STZ-diabetic rats. Insensitivity to glucose in STZ diabetic rats is associated with insensitivity to alloxan. This implies a common defect in the initial recognition site of glucose and alloxan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D000496:Alloxan; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine