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

作者：Scully Michael S; Ort Tatiana A; James Ian E; Bugelski Peter J; Makropoulos Dorie A; Deutsch Heather A; Pieterman El**et J; van den Hoek Anita M; Havekes Louis M; duBell William H; Wertheimer Joshua D; Picha Kristen M^*

来源：Experimental Diabetes Research, 2011, 910159.

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 (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-alpha and darbepoetin-alpha, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

• 出版日期2011