Relationship of Glucose Tolerance to Hepatic Glucokinase Activity

Abstract

Glucokinase, a glucose phosphorylating enzyme found only in liver, has been shown to be both glucose and insulin dependent, as well as glucose specific. Since the liver is freely permeable to glucose, phosphorylation of glucose to glucose-6-phosphate is a potentially rate-limiting step in hepatic glucose utilization and thus an important factor in the determination of oral glucose tolerance. Rats lube fed 0.5 gm. glucose/100 gm. body weight, as the glucose tolerance test, were studied under varying dietary conditions to discover if a correlation between glucokinase activity and glucose tolerance is present. In general, such a relationship was found to exist. Following starvation and following sucrose refeeding, hepatic glucokinase activity was quite low and glucose tolerance curves were significantly elevated when compared to Purina Chow fed rats or glucose refed rats. The glucose refed rats had high hepatic activities of glucokinase when compared with all other groups, and glucose was rapidly cleared from the blood. Fructose refed rats had low levels of hepatic glucokinase activity but did not show glucose intolerance. The explanation for this latter finding remains obscure but several possibilities are discussed.