Figure 1.

The liver–α-cell axis. The liver–α-cell axis constitutes a feedback loop in which circulating amino acids stimulate glucagon secretion from pancreatic α-cells and glucagon in turn controls hepatic amino acid uptake and metabolism, including increased amino acid transport and ureagenesis. The liver–α-cell axis also constitutes a feedback loop in which high levels of circulating glucose inhibit α-cell secretion of glucagon, resulting in decreased hepatic glucose metabolism and subsequent glucose production. In contrast, lower levels of circulating glucose result in increased α-cell secretion of glucagon and increased glucagon-mediated hepatic glucose metabolism, including increased glycogenolysis and gluconeogenesis, and glucose production. A final component of the liver–α-cell axis may be the regulation of hepatic lipid metabolism by increasing β-oxidation and decreasing lipogenesis; however, it is currently not established exactly how, and if, lipids regulate α-cell secretion.