The regulation of glutamine and ketone-body metabolism in the small intestine of the long-term (40-day) streptozotocin-diabetic rat.
The small intestine is the major site of glutamine utilization in the mammalian body. During prolonged (40-day) streptozotocin-diabetes in the rat there is a marked increase in both the size and the phosphate-activated glutaminase activity of the small intestine. Despite this increased capacity, intestinal glutamine utilization ceases in diabetic rats. Mean arterial glutamine concentration fell by more than 50% in diabetic rats, suggesting that substrate availability is responsible for the decrease in intestinal glutamine use. When arterial glutamine concentrations in diabetic rats were elevated by infusion of glutamine solutions, glutamine uptake across the portal-drained viscera was observed. The effect of other respiratory fuels on intestinal glutamine metabolism was examined. Infusions of ketone bodies did not affect glutamine use by the portal-drained viscera of non-diabetic rats. Prolonged diabetes had no effect on the activity of 3-oxoacid CoA-transferase in the small intestine or on the rate of ketone-body utilization in isolated enterocytes. Glutamine (2 mM) utilization was decreased in enterocytes isolated from diabetic rats as compared with those from control animals. However, glutaminase activity in homogenates of enterocytes was unchanged by diabetes. In enterocytes isolated from diabetic rats the addition of ketone bodies or octanoate decreased glutamine use. It is proposed that during prolonged diabetes ketone bodies, and possibly fatty acids, replace glutamine as the major respiratory fuel of the small intestine.
Watford
M
M
Erbelding
E J
EJ
Smith
E M
EM
D000818:Animals; D015256:Coenzyme A-Transferases; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013466:Sulfurtransferases / Q000378:metabolism; D013997:Time Factors
D007657:Ketone Bodies; D005973:Glutamine; D013466:Sulfurtransferases; D015256:Coenzyme A-Transferases; C021460:3-ketoacid CoA-transferase; D005972:Glutaminase