REGULATION OF HEPATIC GLUTAMINASE IN THE STREPTOZOTOCIN-INDUCED DIABETIC RAT

The liver of diabetic animals removes increased quantities of glutamin e. We therefore examined factors that affect hepatic glutaminase activ ity in hepatocytes and mitochondria. Glutamine use, through glutaminas e, was measured in isolated rat hepatocytes by monitoring the producti on of (CO2)-C-14 from [1-C-14]glutamine. Hepatocytes from streptozotoc in-induced diabetic rats use glutamine more rapidly than do hepatocyte s from normal or insulin-maintained diabetic rats. Glutamine use in al l of these hepatocytes was stimulated by glucagon and epinephrine. Glu taminase activity, assayed in broken mitochondrial membranes, was incr eased similar to 2.5-fold in diabetic rats. The sensitivity of glutami nase, measured in intact liver mitochondria, to phosphate was markedly left-shifted in mitochondria from diabetic rats compared with those f rom controls. In fact, glutaminase was increased 10-fold at 2.5 mmol/l phosphate compared with controls. This increased sensitivity of gluta minase to physiological concentrations of phosphate is characteristic of its hormonal activation. Therefore, activation of glutaminase plays a major role in diabetes and is as important as increases in its tota l enzyme amount in determining the increased glutamine uptake in diabe tes.