FIGURE 6.

The adipocyte-hepatocyte axis and insulin suppression of gluconeogenesis. A: in the fasted state, the adipocyte releases nonesterified fatty acids (NEFA) into the circulation. Within the hepatocyte, NEFA are oxidized to mitochondrial acetyl CoA, an allosteric activator of pyruvate carboxylase (PC). PC drives gluconeogenic flux. This, together with net glycogenolysis, facilitates hepatic glucose production (HGP) during fasting. B: during insulin stimulation (e.g., postprandially), both direct and indirect effects of insulin suppress HGP. Adipocyte insulin signaling suppresses lipolysis, decreasing plasma NEFA concentrations, hepatic mitochondrial acetyl CoA concentrations, PC activity, and gluconeogenic flux. Simultaneously, direct insulin action on the hepatocyte promotes net glycogen synthesis. Both processes enable insulin to rapidly and potently suppress net HGP.