Evidence for a Rapidly Reversible Effect of Previous Hyperglycemia

In perfused pancreas of rats rendered diabetic by streptozotocin injection (STZ) during neonatal age the insulin response to 27mM glucose was significant but impaired. It was unaffected by the alpha adrenergic blocker phentolamine. When 27mM 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.