Figure 5. Integrated summary of insulin kinetics after glucose ingestion.

Values represent the mean rates (in pmol/min) for β cell insulin secretion, tissue insulin extraction, and insulin accumulation in the systemic circulation, assessed for 3 hours after ingestion of a 75-g glucose drink. Insulin secretion by the pancreas into the portal circulation increased progressively from the lean-NL to the obese-NL to the obese-NAFLD groups. In addition, a large portion of insulin that entered the portal circulation was not immediately removed by the liver and extrahepatic tissues and was recycled back to the liver via the portal vein and hepatic artery, so the total amount of insulin delivered to the liver (newly secreted and recycled insulin) also increased progressively from the lean-NL to the obese-NL to the obese-NAFLD groups. Although the fractional hepatic extraction of delivered insulin progressively decreased, the rate of total hepatic insulin extraction progressively increased from the lean-NL to the obese-NL to the obese-NAFLD groups. However, the rate of hepatic insulin extraction plateaued when the delivery of insulin to the liver was high, as in the obese-NL and obese-NAFLD groups, because of a saturable hepatic insulin transport system. Most of the insulin that passes through the liver and enters the systemic circulation is recycled back to the liver, and a progressively increasing amount of insulin was removed by extrahepatic tissues (primarily the kidneys and skeletal muscle) in subjects in the lean-NL, obese-NL, and obese-NAFLD groups. A small portion of insulin that entered the systemic circulation (posthepatic insulin) was not removed by 180 minutes after glucose ingestion and was responsible for the increase in plasma insulin concentration above baseline at the 180-minute time point.