INS and Insulin resistance: To elucidate if the age-related alteration in metabolism and glucose homeostasis could be related with insulin resistance in the brainstem with age, we administered insulin via i.c.v. injection and evaluated the phosphorylation of IR and Akt, major markers of insulin signaling, in mice of 3, 6, and 12 months of age after 30 min of treatment (Fig. 2A).