Selective Downregulation of the High–Molecular Weight Form of Adiponectin in Hyperinsulinemia and in Type 2 Diabetes

OBJECTIVE—Adiponectin is an adipocyte-specific secretory protein found in circulation in several different forms and is present at significantly lower levels in the plasma of diabetic patients compared with that of insulin-sensitive individuals. We wanted to test whether insulin per se is a contributing factor toward lower plasma adiponectin concentrations and, if so, whether the splanchnic bed contributes to this phenomenon. RESEARCH DESIGN AND METHODS—We sampled femoral artery and hepatic venous samples and measured the high–molecular weight (HMW) and low–molecular weight (LMW) fractions of adiponectin in 11 type 2 diabetic and 7 nondiabetic subjects matched for age, sex, and BMI during basal conditions and during a hyperglycemic (∼9.5 mmol/l) hyperinsulinemic (∼700 pmol/l) clamp. RESULTS—Under these conditions, total arterial adiponectin, HMW, and the ratio of HMW to total adiponectin all were lower (P < 0.01) in the diabetic versus nondiabetic subjects, whereas the LMW form did not significantly differ. Under hyperinsulinemic conditions, total adiponectin levels dropped, primarily due to a reduction of the HMW form, whereas LMW forms were not significantly affected. CONCLUSIONS—HMW adiponectin and the ratio of HMW to total adiponectin are lower in individuals with diabetes than in nondiabetic subjects. We conclude that HMW adiponectin is downregulated in hyperinsulinemia and type 2 diabetes.