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Selective Downregulation of the High Molecular Weight form (HMW) of Adiponectin in Hyperinsulinemia and in Type 2 Diabetes: Differential Regulation from Non-diabetic Subjects

¹Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905
²Department of Cell Biology
⁴Medicine, Division of Endocrinology
⁵Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
³Current address: Department of Internal Medicine, Columbia University and New York-Presbyterian Hospital, New York, NY, USA
⁶ Current address: Touchstone Diabetes Center, Department of Internal Medicine-The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-9077

Correspondence: basu.rita{at}mayo.edu

Objective:Adiponectin is an adipocyte-specific secretory protein that is found in circulation in several different forms and is present at significantly lower levels in the plasma of diabetic patients compared to insulin sensitive individuals. We wanted to test whether insulin per se is a contributing factor towards lower plasma adiponectin concentrations and if so, whether the splanchnic bed contributes to this phenomenon.

Research Design and Methods:To do so, we sampled femoral artery and hepatic venous samples and measured the high molecular weight (HMW) and low molecular weight (LMW) fraction of adiponectin in 11 type 2 diabetic and 7 non-diabetic subjects matched for age, gender and body mass index 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 S_A ratio of HMW/total adiponectin all were lower (p<0.01) in the diabetic versus non-diabetic 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/total adiponectin are lower in people with diabetes as compared to non-diabetic subjects. We conclude that HMW adiponectin is downregulated in hyperinsulinemia and type 2 diabetes.

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