PERSISTENCE OF DISTURBED ADIPOCYTE METABOLISM IN STREPTOZOCIN-INDUCEDDIABETIC RATS DESPITE NEAR-EUGLYCEMIA WITH PHLORHIZIN

It is widely accepted that hyperglycemia per se incites and perpetuate s the diabetic state by adverse effects on beta cell insulin secretion and peripheral insulin action. Examination of the latter locus has re vealed glucose-related abnormalities in facilitated glucose transport. Beyond the plasma membrane, however, there is scant data examining wh ether hyperglycemia influences important intracellular metabolic event s. We recently described a sizable reduction in post-transport, in sit u metabolism in permeabilized fat cells from streptozocin-induced diab etic rats. Of importance, the diabetes-related deficit was entirely am eliorated by insulin therapy. In this study we examined whether hyperg lycemia per se contributes to this altered intracellular metabolic eff ect. By infusing phlorizin, near euglycemia was achieved for at least four days in streptozocin-induced diabetic rats. The phlorizin-treated diabetic rats had improved (intact cell) rates of insulin-stimulated 2-deoxyglucose uptake. Despite this, permeabilized fat cell studies re vealed no improvement or deterioration in diabetic intracellular metab olism as measured by both the oxidation of [6-C-14]glucose-6-phosphate via the citric acid cycle or its incorporation into triglyceride. We conclude that hypsinsulinemia, and not hyperglycemia, mediates the dis turbance in porous diabetic adipocyte cellular metabolism.