Glycogenesis mechanisms

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

The hormonal mechanisms of action to regulate glycogenesis and glycogenol-ysis involve reversible phosphorylation of the critical enzymes glycogen synthase and phosphorylase, respectively (Figure 6—6). 

As work with vanadium compounds and diabetes in cell system has continued, it has become clear that there are also insulin-independent mechanisms at work. One insulin-independent signal transduction pathway appears to be involved in glycogen metabolism reactions in rat adipocytes [137] that also involve PI-3K. A major difference was that only vanadate promoted glycogenesis through the activation of a cytosolic protein tyrosine kinase, which was mediated in an insulin receptor-independent manner. 

The glycogenesis and glycogenolysis enzymes subject to hormonal control are glycogen synthase and phosphorylase, respectively. Briefly, glycogen synthase is inhibited by high cellular cAMP and Ca2+ levels, whereas phorphorylase is stimulated. The mechanisms for accomplishing this are quite complex. 

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