Diabetes, Vol 36, Issue 4 459-464, Copyright © 1987 by American Diabetes Association

ARTICLES

Impaired insulin secretion associated with near normoglycemia. Study in normal rats with 96-h in vivo glucose infusions

JL Leahy, HE Cooper and GC Weir

We have previously demonstrated impaired glucose influence on insulin secretion in normal rats made overtly hyperglycemic with glucose infusions for 48 h. We examined the effects of a 96-h infusion period. Rats received 30, 35, or 50% glucose or 0.45% NaCl at 2 ml/h. The plasma glucose in the 30 and 35% rats peaked at 24 h but then returned to normal by 72 h. A peak followed by a gradual fall also occurred in the 50% rats, but significant hyperglycemia was maintained throughout. beta-Cell responsiveness to glucose was assessed with the perfused pancreas by examining the effect of altering the perfusate glucose concentration on insulin release. Insulin secretion remained intact in the 30% rats, but the response to a glucose increase was blunted in the 35% group and totally absent in the 50% rats. In a second protocol, glucose influence on arginine-stimulated insulin release was tested by adding 10 mM arginine to the perfusate and administering it with 2.8 and 16.7 mM glucose. The ability of the different glucose backgrounds to influence the insulin response decreased as the level of infused glucose rose. On the other hand, when phloridzin was added to 50% glucose during the second 48 h of infusion, glucose modulation of insulin release was completely restored. These data indicate that during a period of overt hyperglycemia, beta-cell defects can fully evolve within 48 h in the rat. Thereafter, they are maintained by the glucose infusion even though the plasma glucose level returns to near normal. Continued minor stimulation of the beta-cell may be the responsible factor.
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