The role of the liver in the modulation of glucose and insulin in non alcoholic fatty liver disease and type 2 diabetes

In this review we have discussed how the liver plays a central role in the regulation of glucose metabolism and in insulin clearance. Both non-alcoholic fatty liver disease (NAFLD) and diabetes (T2D) are characterized by high plasma insulin concentrations, hepatic insulin resistance, high hepatic glucose production (HGP), in particular gluconeogenesis (GNG), that are increased proportionally to fasting hyperglycemia, while postprandial hyperglycemia is due to impaired suppression of HGP by insulin, and reduced hepatic glycogen storage. The liver acts also as a modulator of peripheral insulin since most of insulin secreted by the pancreas is cleared by the liver during the first pass. Hepatokines and hepatic lipids can act in either autocrine or paracrine way and can be responsible of the changes in insulin sensitivity and alterations in glucose metabolism.