Effects of glucagon-like peptide 1 on the hepatic glucose metabolism

Glucagon-like peptide 1 has important actions in lowering blood glucose, both through its incretin action and by regulating other systems affecting glucose metabolism. There is good evidence that the coordinate regulation of islet hormones by GLP-1 has significant effects on hepatic glucose metabolism, and this likely contributes to the potent effect of GLP-1 on fasting hyperglycemia in diabetic patients. More controversial are potential effects of GLP-1 on hepatic glucose production or storage independent of insulin and glucagon. There are data from in vitro studies supporting an effect of GLP-1 to promote glycogen synthesis in hepatocytes, and several in vivo studies suggesting that GLP-1 has independent effects on hepatic glucose uptake and/or production. However, these findings must be considered against a backdrop of studies that have not demonstrated islet-independent actions of GLP-1. This paper will review the current literature addressing hepatic effects of GLP-1 and identify important gaps in the knowledge base for this topic.