Reciprocal Variations in Insulin-Stimulated Glucose Uptake and Pancreatic Insulin Secretion in Women With Normal Glucose Tolerance

Objective: Maintenance of normal glucose tolerance is achieved in subjects with a wide range of insulin sensitivity. It follows, therefore, that the body must possess a sensor mechanism that assesses the body's sensitivity to insulin and appropriately adjusts the secretion of insulin to maintain normal glucose homeostasis. We evaluated the relation between insulin action and insulin secretion. Methods: Euglycemic hyperinsulinemic clamp (1 mU/kg · minute) and hyperglycemic clamp (+ 125 mg/dL) studies were performed in 32 non-obese women with normal oral glucose tolerance tests. The subjects were stratified into quartiles based upon their insulin-mediated rate of glucose uptake during the eulgycemic insulin clamp. Results: Total body glucose disposal varied threefold, ranging from 4.00 to 11.18 mg/kg · minute. A significant inverse relation (r = -0.50, P <.01) was noted between the rate of total body insulin-mediated glucose disposal (insulin clamp) and the total plasma insulin response during the hyperglycemic clamp. Women in the lowest quartile of insulin sensitivity (mean glucose uptake 5.07 ± 0.20 mg/kg · minute) had the highest plasma insulin response during the hyperglycemic clamp (109 ± 20 μU/mL). In contrast, women in the highest quartile of insulin sensitivity (glucose uptake 9.90 ± 0.38 mg/kg · minute) had the lowest plasma insulin response during the hyperglycemic clamp (55 ± 16 μU/mL; P <.001 versus the lowest quartile). Conclusions: These results demonstrate that among subjects with normal glucose tolerance, there exists a large variation in both insulin-mediated glucose uptake and pancreatic insulin secretion. Nonetheless, normal glucose tolerance is maintained because of a finely regulated balance, which couples the demand for insulin secretion by the pancreatic beta cells to the level of whole-body insulin sensitivity.