Signals adapting the beta cells to changes in insulin sensitivity

Insulin sensitivity and secretion are related in a curvilinear inverse asymptotic function. However, the signaling factors mediating this relation are not known. In this study, we explored whether circulating glucose, lipids or two adipocyte-derived hormones, leptin and adiponectin, are related to the curvilinear function between insulin sensitivity and secretion in subjects with normal glucose tolerance. Thereby, insulin secretion (2-5-min insulin response to intravenous arginine) and insulin sensitivity (euglycemic, hyperinsulinemic clamp) were established in 68 healthy women, aged 61 years. We confirmed the curvilinear relation between insulin sensitivity and insulin secretion (r = -0.71, P < 0.001). To quantify the ability of the beta cells to secrete insulin for balancing a change in insulin sensitivity, we introduce the beta cell compensation index (BCI) by dividing insulin secretion by insulin sensitivity. This index correlated significantly with circulating triglycerides, leptin and adiponectin as well as BMI, but not fasting or 2-h glucose. A multivariate stepwise regression analysis using these variables as independent variables and lg BCI as the dependent variable revealed that leptin (r = 0.54, P < 0.001) and adiponectin (r = -0.33, P = 0.008) independently contributed to lg BCI (R-2 of the model = 0.19m, P = 0.038). The study, therefore, suggests that adipocyte-derived hormones contribute to the beta cell compensation to insulin resistance. (C) 2002 Elsevier Science B.V. All rights reserved.