Matched rates of insulin infusion and secretion and concurrent tracer-determined rates of glucose appearance and disappearance in fasting dogs

Abstract

The endogenous secretion rate of insulin in the dog was matched by an intraportal infusion of exogenous pork insulin at a rate of 12 milliunits/kg h following removal of the remnant pancreatic autograft. Both homeostasis and a dynamic steady state for glucose were observed. An apparent functional relationship between the infusion rates of insulin (7.2–16.4 milliunits/kg h) and the tracer-determined rates of glucose appearance and disappearance was found following graft removal, but not in the diabetic dog after reduction of hyperglycemia. With rates of insulin infusion less than 12 milliunits/kg h the rate of glucose appearance increased and the rate of its disappearance decreased, causing glucose accumulation. Opposite changes were observed with insulin infusion rates from 15 to 156 milliunits/kg h. When the infusion was switched from the portal to a nonsplanchnic vein the dog was more sensitive to the hypoglycemic action of insulin. The switch-off of insulin infusions, maintained for 4.5–7.0 h in the depancreatized dog at different glucose levels, resulted within 2 min in a rise in plasma glucose concentration caused by both underutilization and overproduction of glucose. Overproduction of glucose was still observed 15 h thereafter, when a new steady state was being approached. It is postulated that in the fasting dog at normal glucose levels a continuous insulin secretion of 12 milliunits/kg h is indispensable for the apparent negative feedback mechanism to maintain glucose near the dynamic steady state. In the absence of insulin, the apparent feedback mechanism becomes functional again but at high glucose levels.