In perfused pancreas of rats rendered diabetic by streptozotocin injection (STZ) during neonatal age the insulin response to 27 mM glucose was significant but impaired. It was unaffected by the alpha adrenergic blocker phentolamine. When 27 mM mannoheptulose was added simultaneously with 27 mM glucose, insulin release was inhibited, but less promptly than in pancreases from non-diabetic rats. When mannoheptulose was introduced 15 min after starting perfusion with 27 mM glucose, inhibition was apparent in non-diabetic rats, but not in STZ. In non-diabetic rats perfusion without glucose for 40 min failed to affect the subsequent response to 27 mM glucose. Conversely, in STZ, glucose omission enhanced 3.7-fold the response to 27 mM glucose. Insulin release in response to 3-isobutyl-1-methylxanthine (IBMX) was more marked in STZ than in non-diabetic rats. After glucose omission the IBMX-induced response was, however, reduced (67%) in STZ, but not significantly (7%) in non-diabetic rats.Thus, glucopenia in vitro sensitizes B cells of STZ to glucose, but desensitizes them to IBMX. Abnormal responsiveness may be linked to metabolic consequences of B cell fuel abundance.
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.
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