A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

• Published in: Journal of diabetes research Vol. 2011; no. 2011; pp. 1 - 10
• Main Authors: duBell, William H., Wertheimer, Joshua D., Picha, Kristen M., van den Hoek, Anita M., Pieterman, Elsbet J., Deutsch, Heather A., Makropoulos, Dorie A., Bugelski, Peter J., James, Ian E., Ort, Tatiana A., Scully, Michael S., Havekes, Louis M.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2011
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2011/910159

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 14C-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.