Hyperglycemia prevents the suppressive effect of hyperinsulinemia on plasma adiponectin levels in healthy humans.

Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for the downregulation of adiponectin. Insulin decreases adiponectin levels in humans. The effect of hyperglycemia is unknown. To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose). Adiponectin concentrations and high-molecular-weight (HMW)-to-total adiponectin ratio were measured at the start and end of the 6-h clamps. After the 6-h study period, total plasma adiponectin levels were significantly (P = 0.045) decreased by 0.63 microg/ml in the lower insulinemic-euglycemic clamp (clamp 1). In both euglycemic groups (clamps 1 and 2) adiponectin concentrations significantly declined (P = 0.016) over time by 0.56 microg/ml, whereas there was no change in both hyperglycemic groups (clamps 3 and 4) (P = 0.420). In none of the clamps did the ratio of HMW to total adiponectin change. We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l. Hyperglycemia prevents the suppressive effect of insulin. This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients.