Fig. 1.

Acute central insulin or IGF-1 can restore whole-body insulin action in old rats to more youthful levels a old rats have greater total body weight compared with young rats, as well as b increased VF. c–d Approximately 4-h fasting plasma insulin and IGF-1 levels were not significantly different between young (n = 10) and old rats (n = 11), although e plasma IGFBP-3 levels were reduced with age. f Hyperinsulinemic-euglycemic clamps were performed with concomitant ICV infusion with aCSF (young n = 8; old n = 11), old IGF-1 (n = 16), or old insulin (n = 8). The glucose infusion rate (GIR) required to maintain euglycemia was reduced in old aCSF rats compared with young controls whereas both insulin and IGF-1 infusion in old rats restored GIR to young levels. g–h Suppression of hepatic glucose production (HGP) under hyperinsulinemia did not differ with age, but the ability of insulin to stimulate glucose disposal rates (Rd) was substantially lower in old animals. However, ICV insulin was able to both enhance suppression of HGP, and increase glucose disposal, relative to old control animals, was likewise lower under basal conditions in old relative to young aCSF rats but was partially restored in IGF-1 and insulin rats; under clamped conditions, old IGF-1 and old insulin rats displayed lower HGP than young aCSF animals. h Glucose disposal rate (R_d) was lower in old compared with young rats but was restored to levels comparable to young aCSF rats in old IGF-1 and old insulin rats under basal conditions; old IGF-1 levels were intermediate with clamp, whereas old insulin R_d was comparable to that observed in young aCSF rats. Young versus old comparisons were conducted using an independent sample t-test while clamp data were analyzed via one-way ANOVA. Vertical bars and lines represent mean ± SE. Different letters indicate significant differences between groups determined by Tukey honest significant differences (HSD) *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001