Regulation of net hepatic glucose uptake: interaction of neural and pancreatic mechanisms

Insulin and glucagon levels, the mass of glucose presented to the liver and the portal signal are important regulators of the liver's response to glucose delivery. The portal signal not only serves to direct glucose into the liver but also appears to stimulate its deposition in glycogen. Moreover, the portal signal impacts on tissues other than the liver: intraportal glucose delivery is associated with changes in glucose uptake by nonhepatic tissues and neurally-mediated enhancement of pancreatic insulin secretion. Our current understanding of the neural control of hepatic glucose metabolism includes a tonic block to the entry of glucose into the liver, probably mediated both by sympathetic neural activity and by a low insulin:glucagon ratio. An increase in the portal vein glucose level is detected by sensors in the portal region, which cause a decrease in the firing rate in the hepatic branch of the vagus nerve. The change in the afferent firing rate is processed in the hypothalamus and instigates a change in the efferent firing rate in the hepatic and pancreatic branches of the vagus (with corresponding increases in insulin secretion and net hepatic glucose uptake). The portal signal thus relieves the sympathetic inhibition of hepatic glucose uptake and enhances hepatic glucose uptake directly by stimulating the parasympathetic innervation to the liver and indirectly by enhancing insulin release.