Hepatic glucose metabolism in humans—its role in health and disease

Abstract

The liver is mainly responsible for maintaining normal concentrations of blood glucose by its ability to store glucose as glycogen and to produce glucose from glycogen breakdown or gluconeogenic precursors. During the last decade, new techniques have made it possible to gain further insight into the turnover of hepatic glucose and glycogen in humans. Hepatic glycogen varies from approximately 200 to approximately 450 mM between overnight fasted and postprandial conditions. Patients with type-1 diabetes (T1DM), type 2 diabetes (T2DM) or partial agenesis of the pancreas exhibit increased endogenous glucose production and synthesize only 25-45% of hepatic glycogen compared with non-diabetic humans. This defect can be partly restored in T1DM by combined long- and short-term optimized treatment with insulin. In T2DM, increased gluconeogenesis was identified as the main cause of elevated glucose production and fasting hyperglycaemia. These patients also exhibit augmented intracellular lipid accumulation which could hint at a link between deranged glucose and lipid metabolism in insulin-resistant states.