Implications of distinct inhibitory effects of N-acetylglucosamine on glucose uptake by an isolated perfusion system incorporating erythrocytes with livers from fed and 48-hour fasted rats.
Net glucose uptake in a perfusion system including erythrocytes and isolated livers from fed rats was inhibited by N-acetylglucosamine (GlcNAc), a competitive inhibitor of glucokinase. Net glucose uptake also occurred in the system incorporating livers from 48-h fasted rats, but its inhibition by GlcNAc did not. This distinction could not be explained on the basis of a different sensitivity of glucokinase from fasted compared with fed rats to inhibition by GlcNAc. Nor could it be rationalized based on several other hepatic enzymes possibly involved in glucose utilization or production. Because erythrocytes were included in our system, other explanations were sought related to the total enzymic environment. The involvement of an indirect pathway including glycolysis of glucose to lactate in erythrocytes followed by conversion of this lactate to glucose-6-P and then glycogen in liver was considered. This pathway contributed no more than 17% to total net glucose uptake in the system incorporating livers from fed rats. This per cent contribution increased when hepatic glucokinase was reduced by fasting or through inhibition by GlcNAc. However, it was too small to explain observed overall rates of net glucose uptake. We propose that the presence of erythrocytes may also promote a greater net glucose uptake by the direct hepatic pathway. An enhanced inhibition of hepatic glucose-6-P hydrolysis by some intermediate metabolite generated in the presence of lactate infusion from erythrocytes may promote net glucose uptake independently of the mechanism of residual hepatic glucose phosphorylation. This may explain why we and others who have employed liver perfusion systems including erythrocytes have seen greater net glucose uptake than have workers using systems devoid of erythrocytes.
K A
KA
Sukalski
R C
RC
Nordlie
D000117:Acetylglucosamine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D004912:Erythrocytes / Q000378:metabolism*; D005215:Fasting; D005941:Glucokinase / Q000302:isolation & purification / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives*; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000302:isolation & purification / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose; D005944:Glucosamine; D000117:Acetylglucosamine