Postprandial physiology

Alan Cherrington, Nashville, TN, examined the effect of insulin to inhibit hepatic glucose production. Using a dog preparation with somatostatin to block insulin and glucagon production and administration of insulin and glucagon into the portal vein, decreasing portal insulin to levels similar to those in the arterial circulation immediately increased hepatic glucose production via glycogenolysis, which was sustained over a period of several hours, with consequent hyperglycemia. There is a steep inverse dose-response curve of hepatic glucose production versus hepatic sinusoidal insulin levels. Tripling insulin quickly turns off hepatic glucose production. Glucose utilization by the liver in response to increasing insulin levels has a longer time course, taking several hours to reach maximal levels. This response is much less sensitive to changes in insulin levels than hepatic glucose production, and normal basal hepatic glucose utilization is very low. Muscle is less sensitive on a molar basis than in the liver, so that a tripling of insulin levels causes only a 50% increase in glucose utilization, compared with the more than sixfold increase in glucose uptake under maximal stimulation.

Comparing the effects of first-phase and second-phase insulin release in response to glucagon, the former more potently inhibits glucose production. Insulin levels show similar first- and second-phase responses to a hyperglycemic clamp, and elimination of the first-phase insulin response leads to much greater hepatic glucose production, although it has little effect on glucose utilization. A recent study with nateglinide similarly showed a rapid insulin response and marked lessening of postprandial hyperglycemia (1). When intraduodenal glucose is given with dogs having somatostatin and portal catheters, a first-phase …