May 1, 1987Journal of Clinical Investigation814 citationsOpen Access
Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.
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Key Points
- This research aims to explore how hyperglycemia contributes to insulin resistance and the effect of phlorizin treatment on insulin sensitivity.
- Examined five groups of rats: sham-operated, diabetic with glucose intolerance, phlorizin-treated diabetic, control treated with phlorizin, and re-evaluated phlorizin-treated diabetic after discontinuation.
- Assessed insulin sensitivity using the euglycemic hyperinsulinemic clamp technique in awake rats.
- Noted changes in insulin-mediated glucose metabolism pre and post phlorizin treatment.
- Insulin-mediated glucose metabolism was reduced by approximately 30% in diabetic rats (P<0.001).
- Phlorizin treatment normalized insulin sensitivity in diabetic rats without altering insulin levels.
- Discontinuation of phlorizin in previously treated diabetic rats resulted in renewed insulin resistance.
Abstract
Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizin-treated controls; and group V, phlorizin-treated diabetic rats restudied after discontinuation of phlorizin. Insulin sensitivity was assessed with the euglyemic hyperinsulinemic clamp technique in awake, unstressed rats. Insulin-mediated glucose metabolism was reduced by approximately 30% (P less than 0.001) in diabetic rats. Phlorizin treatment of diabetic rats completely normalized insulin sensitivity but had no effect on insulin action in controls. Discontinuation of phlorizin in phlorizin-treated diabetic rats resulted in the reemergence of insulin resistance. These data demonstrate that a reduction of beta-cell mass leads to the development of insulin resistance, and correction of hyperglycemia with phlorizin, without change in insulin levels, normalizes insulin sensitivity. These results provide the first in vivo evidence that hyperglycemia per se can lead to the development of insulin resistance.
Cite This Study
Rossetti et al. (1987) studied this question.