Effect of diabetic ketosis on jejunal glutaminase.
The intestine is capable of shifting its major fuel source from glutamine in the fed animal to ketone bodies in the fasted animal. Glutaminase (EC 3.5.1.2), the entry enzyme of glutamine oxidation, was examined for its function as a determinant in the utilization of jejunal fuel during diabetes and fasting. Male Sprague-Dawley rats were made ketotic to varied degrees by either fasting or the induction of diabetes with graded doses of streptozotocin (SZ). Specific activity of glutaminase was decreased in the diabetic animals to 64% (p less than 0.05) of controls in the group receiving 110 mg/kg SZ and 82% of controls in the group receiving 65 mg/kg SZ and to 78% (p less than 0.05) of controls in the fasted animals. The activity of glutaminase in the small intestine was negatively correlated to the concentration of beta-hydroxybutyrate in the plasma (r = -0.97, p less than 0.025) and jejunum (r = -0.92, p less than 0.05) for the four groups of animals. Specific activity of glutaminase was decreased in all cell types isolated along the villus-crypt axis of the small intestine from diabetic and fasted rats compared with control rats. The quantity of glutaminase-protein was determined by a dot immunobinding assay using an antibody to purified glutaminase. The activity of glutaminase relative to immunoreactive glutaminase-protein was significantly decreased (p less than 0.05) to 53% of control values in the 110 mg/kg SZ group, 77% in the 65 mg/kg SZ group, and 70% in the fasted group. These data indicate that an inactivation of glutaminase-protein may play a role in the ability of the intestine to shift its fuel source from glutamine to ketone bodies during diabetes and fasting.
D020155:3-Hydroxybutyric Acid; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D016883:Diabetic Ketoacidosis / Q000201:enzymology*; D005215:Fasting; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006885:Hydroxybutyrates / Q000097:blood / Q000378:metabolism; D007583:Jejunum / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006885:Hydroxybutyrates; D005973:Glutamine; D005972:Glutaminase; D020155:3-Hydroxybutyric Acid