Regulation of hepatic glutaminase in the streptozotocin-induced diabetic rat

Diabetes
S A SquiresJ T Brosnan

Abstract

The liver of diabetic animals removes increased quantities of glutamine. We therefore examined factors that affect hepatic glutaminase activity in hepatocytes and mitochondria. Glutamine use, through glutaminase, was measured in isolated rat hepatocytes by monitoring the production of 14CO2 from [1-(14)C]glutamine. Hepatocytes from streptozotocin-induced diabetic rats use glutamine more rapidly than do hepatocytes from normal or insulin-maintained diabetic rats. Glutamine use in all of these hepatocytes was stimulated by glucagon and epinephrine. Glutaminase activity, assayed in broken mitochondrial membranes, was increased approximately 2.5-fold in diabetic rats. The sensitivity of glutaminase, measured in intact liver mitochondria, to phosphate was markedly left-shifted in mitochondria from diabetic rats compared with those from controls. In fact, glutaminase was increased 10-fold at 2.5 mmol/l phosphate compared with controls. This increased sensitivity of glutaminase 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 total enzyme amount in determining the increased glutamine upt...Continue Reading

Citations

Jan 1, 1995·Advances in Enzyme Regulation·J T BrosnanS A Squires
Apr 6, 2002·Nutrition·M WatfordPriya Raman
Feb 26, 2000·Diabetic Medicine : a Journal of the British Diabetic Association·B H WolffenbuttelR N Patwardhan
May 25, 2002·Journal of Toxicology and Environmental Health. Part a·F Murat GörgünEmine Kökogu
Sep 25, 2004·Canadian Journal of Physiology and Pharmacology·Enoka P WijekoonJ T Brosnan
Jan 9, 2010·Journal of Biomedical Science·Jurandir Fernando ComarA Bracht
Jul 6, 2010·Life Sciences·Aparajita Dey, Kavitha Swaminathan
Mar 11, 2000·American Journal of Physiology. Endocrinology and Metabolism·D O'SullivanM E Brosnan

Related Concepts

Metazoa
Carbon Dioxide
Carbon Radioisotopes
Streptozotocin Diabetes
Epinephrine Acetate
Glucagon
Phosphate-Activated Glutaminase
D-Glutamine
Liver
Mitochondria, Liver

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