1. A novel EPO receptor agonist improves glucose tolerance via glucose uptake in skeletal muscle in a mouse model of diabetes.
- Author
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Scully MS, Ort TA, James IE, Bugelski PJ, Makropoulos DA, Deutsch HA, Pieterman EJ, van den Hoek AM, Havekes LM, Dubell WH, Wertheimer JD, and Picha KM
- Subjects
- Animals, Darbepoetin alfa, Diabetes Mellitus, Experimental etiology, Diabetes Mellitus, Experimental physiopathology, Dietary Fats adverse effects, Disease Models, Animal, Dose-Response Relationship, Drug, Epoetin Alfa, Erythropoietin analogs & derivatives, Erythropoietin pharmacology, Glucose Clamp Technique, Glucose Tolerance Test, Insulin Resistance physiology, Male, Mice, Mice, Inbred C57BL, Obesity complications, Obesity etiology, Obesity metabolism, Recombinant Proteins, Time Factors, Diabetes Mellitus, Experimental metabolism, Glucose metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Receptors, Erythropoietin agonists, Recombinant Fusion Proteins pharmacology
- 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.
- Published
- 2011
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