Lack of Delay in Hepatic Insulin Transit as Indicated by Concordance of Insulin Secretory and Peripheral Insulin Pulses

The liver is an important site of insulin metabolism and action. It has often been assumed that the liver may diminish the amplitude of the insulin secretory waveform without altering hepatic insulin transit time. However, the significant extraction and metabolism of hepatic insulin has the potential to delay hepatic insulin transit. To examine hepatic insulin transit, we studied the concordance of calculated insulin secretory peaks with peripheral insulin peaks in 12 healthy men of varying body weight and fat distribution. Adiposity was determined by percent body fat, and fat distribution by the waist to hip ratio. Arterialized peripheral venous samples for insulin and C-peptide assays were obtained every 2 minutes for 90 minutes. Pancreatic insulin secretion rates were estimated with individual C-peptide kinetics using a two-compartment model. Concordance between insulin secretory peaks and peripheral insulin peaks was assessed by the hypergeometric probability model. A signficant concordance between secretory and peripheral insulin pulses was demonstrated in seven of 12 subjects (P < .00001). The mean pulse intervals for insulin secretion were similar to the mean pulse intervals for peripheral insulin. The degree of concordance between the insulin secretory peaks and peripheral insulin pulses was unrelated to adiposity or body fat distribution. Significant synchronicity exists between insulin secretory peaks and peripheral insulin peaks in healthy men. We conclude that despite signficant hepatic insulin extraction and metabolism, hepatic insulin transit may not be delayed in healthy men.