A novel EPO receptor agonist improves glucose tolerance via glucose uptake in skeletal muscle in a mouse model of diabetes

Exp Diabetes Res. 2011:2011:910159. doi: 10.1155/2011/910159. Epub 2011 Jun 30.

Abstract

Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of (14)C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

MeSH terms

  • Animals
  • Darbepoetin alfa
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dietary Fats / adverse effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Epoetin Alfa
  • Erythropoietin / analogs & derivatives
  • Erythropoietin / pharmacology
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Insulin Resistance / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Obesity / complications
  • Obesity / etiology
  • Obesity / metabolism
  • Receptors, Erythropoietin / agonists*
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Proteins
  • Time Factors

Substances

  • CNTO 530
  • Dietary Fats
  • Receptors, Erythropoietin
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Erythropoietin
  • Darbepoetin alfa
  • Epoetin Alfa
  • Glucose