An adiponectin-like molecule with antidiabetic properties

Endocrinology. 2009 Oct;150(10):4493-501. doi: 10.1210/en.2008-1768. Epub 2009 Jul 16.


Adiponectin increases glucose transport, reduces inflammation, and controls vascular functions. Hence, we propose that treatment with a recombinant globular domain of adiponectin (rgAd110-244) has significant therapeutic potential to treat insulin resistance. Mice were fed for 3 months on a high-fat diet (HFD) to induce insulin resistance, diabetes, and moderate weight gain. The mice were first infused iv with different doses of rgAd110-244 (0.12, 0.4, and 1.2 microg/kg x min) for 5 h. Basal and insulin-sensitive glucose use rates were assessed by the use of a submaximal rate of insulin in the awake free-moving mouse. rgAd110-244 reduced, with dose dependence, epinephrine-induced hyperglycemia and HFD-induced insulin resistance by increasing whole-body glucose use (35% at the highest dose) and glycolysis rates. Similarly, the reduction of plasma free fatty acid concentrations by insulin was dramatically improved. Basal hepatic glucose production was unchanged by rgAd110-244 infusion. This acute rgAd110-244 treatment improved glucose homeostasis and was associated with an increased content of muscle phospho-Akt, glycogen synthase kinase-3beta, and AMP-activated kinase. Second, HFD mice were chronically treated with sc rgAd110-244 injections (10, 30, and 100 microg/kg). Fasting glycemia and insulin-sensitive glucose use were improved by rgAd110-244 at the highest dose at completion of the treatment, with concomitant reduction in body weight gain. We here show for the first time that a recombinant adiponectin fragment (110-244 amino acids called rgAd110-244) is able to treat insulin-resistant diabetes. Our results strongly suggest further pharmacological investigation of rgAd110-244 with the objective of developing a new treatment of insulin-resistant diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / isolation & purification
  • Adiponectin / pharmacology*
  • Adiponectin / therapeutic use
  • Animals
  • Blood Glucose / drug effects*
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / etiology
  • Dietary Fats / adverse effects
  • Epinephrine
  • Fasting / metabolism
  • Hyperglycemia / chemically induced
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin Resistance
  • Lipid Metabolism / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Phosphorylation
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Signal Transduction


  • Adiponectin
  • Blood Glucose
  • Dietary Fats
  • Hypoglycemic Agents
  • Insulin
  • Peptide Fragments
  • Recombinant Proteins
  • adiponectin (110-244), human
  • Epinephrine