title: Abnormal B-cell function in neonatally streptozotocin-diabetic rats: insensitivity to alloxan toxicity.
abstract: 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.
mesh_terms: 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
chemical_list: D007328:Insulin; D000496:Alloxan; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine