The PNS of ob/ob mice displayed reduced Akt activation in response to intrathecal IGF-1. Similar to the results shown for intrathecal insulin, an intrathecal injection of IGF-1 produced a strong activation of Akt in both the DRG and sciatic nerve of nondiabetic mice, but the response was somewhat blunted in the PNS of ob/ob mice. In the DRG (A), there was a significant increase in Akt activation in both the nondiabetic and ob/ob mice; however, the activation level was significantly lower in the DRG from ob/ob mice. In the sciatic nerve (B), IGF-1 stimulation resulted in a significant Akt activation in nondiabetic mice, but not in the ob/ob mice. * = p < 0.05, ** = p < 0.01, *** = p < 0.001. n = 8 nondiabetic PBS, n = 9 nondiabetic IGF-1, n = 7 diabetic PBS, n = 10 diabetic IGF-1.