Adiponectin in insulin resistance: lessons from translational research1234

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Adiponectin is an adipose tissue–secreted endogenous insulin sensitizer, which plays a key role as a mediator of peroxisome proliferator-activated receptor γ action. Adiponectin alters glucose metabolism and insulin sensitivity, exhibits antiinflammatory and antiatherogenic properties, and has been linked to several malignancies. Circulating concentrations of adiponectin are determined primarily by genetic factors, nutrition, exercise, and abdominal adiposity. Adiponectin concentrations are lower in subjects with obesity, metabolic syndrome, and cardiovascular disease. Adiponectin knockout mice manifest glucose intolerance, insulin resistance, and hyperlipidemia and tend to develop malignancies especially when on high-fat diets. Animal studies have also shown beneficial effects of adiponectin in rodents in vivo. Circulating concentrations of adiponectin are lower in patients with diabetes, cardiovascular disease, and several malignancies. Studies to date provide promising results for the diagnostic and therapeutic role of adiponectin in obesity, insulin resistance, diabetes, cardiovascular disease, and obesity-associated malignancies.

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1

From the Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

2

Presented at the symposium ‘‘Novel Therapeutic Advances through the Development of Selective PPARγ Modulators from Bench to Bedside,’’ held at Experimental Biology 2009, New Orleans, LA, 21 April 2009.

3

Supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK079929, R01DK058785, K24DK081913, and 5U01DK057154.

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Address correspondence to CS Mantzoros, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Stoneman 816, Boston, MA 02215. E-mail: [email protected].