Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis

Hepatic glycogen is replenished during the absorptive period postprandially . This repletion is prompted partly by an increased hepatic uptake of gluco se by the liver, partly by metabolite and hormonal signals in the portal ve in and, partly by an increased gluconeogenic flux to glycogen (glyconeogene sis). There is some evidence that the direct formation of glycogen from glu cose and that formed by gluconeogenic pathways is linked. This includes: (i ) the inhibition of all glycogen synthesis, in vivo, when gluconeogenic flu x is blocked by inhibitors; (ii) a dual relationship between glucose concen trations, lactate uptake by the liver and glycogen synthesis (by both pathw ays) which indicates that glucose sets the maximal rates of glycogen synthe sis while lactate uptake determines the actual flux rate to glycogen; (iii) the decrease of both gluconeogenesis and glycogen synthesis by the biguani de, metformin; and (iv) correlations between increased gluconeogenesis and liver glycogen in obese patients and animal models. The degree to which the liver extracts portal glucose is not entirely agreed upon although a prepo nderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. This enzyme may be lin ked to the expression of other enzymes in the gluconeogenic pathway. Perive nous cells in the liver may induce additional gluconeogenesis in the peripo rtal cells by increasing glycolytically produced lactate. A number of poten tial mechanisms therefore exist which could link glycogen synthesis from gl ucose and gluconeogenic substrate. Copyright (C) 2001 John Wiley & Sons, Lt d.