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J Clin Invest. 1986 Mar;77(3):908-15.

Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions.


We have proposed that chronic hyperglycemia alters the ability of glucose to modulate insulin secretion, and have now examined the effects of different levels of hyperglycemia on B cell function in normal rats using chronic glucose infusions. Rats weighing 220-300 g were infused with 0.45% NaCl or 20, 30, 35, or 50% glucose at 2 ml/h for 48 h, which raised the plasma glucose by 18 mg/dl in the 30% rats, 37 mg/dl in the 35% rats, and 224 mg/dl in the 50% group. Insulin secretion was then examined using the in vitro isolated perfused pancreas. Glucose-induced insulin secretion remained intact in the normoglycemic 20% glucose rats and it was potentiated in the mildly hyperglycemic 30% glucose rats. However, with even greater hyperglycemia in the 35% glucose group the insulin response to a high glucose perfusate was severely blunted, and it was totally lost in the most hyperglycemic 50% glucose rats. In a second protocol that examined glucose potentiation of arginine-stimulated insulin release, a similar impairment in the ability of glucose to modulate the insulin response to arginine was found with increasing levels of chronic hyperglycemia. On the other hand, the ability of a high glucose concentration to inhibit arginine-stimulated glucagon release was preserved in all glucose-infused rats, but the glucagon levels attained in response to the arginine at 2.8 mM glucose were much less in the 50% glucose rats than in all the other groups. These data clearly show that after 48 h of marked hyperglycemia, glucose influence upon insulin secretion in the rat is severely impaired. This model provides a relatively easy and reproducible method to study the effects of long-term hyperglycemia on B cell function.

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