Figure 1.

(a) Decreased porosity of the LSEC with age from scanning electron micrographs (n = 5 young and 5 old F344 rats P = 0.006). (b) Sample scanning electron micrographs of the LSEC to clearly illustrate the difference between young and defenestrated old rats, original micrographs taken at 15 000× magnification (fenestrations are indicated by an *). (c) There is a 20% reduction in the fractional volume of distribution of insulin with age (n = 9 young and 10 old F344 rats, P = 0.01) (d) MID outflow curves for insulin and the extracellular marker sucrose. Insulin exits the liver prior to sucrose in the old animals, indicating a restricted access to the entire extracellular space with age‐related defenestration. (e) ¹⁴C‐insulin uptake by the liver was found to be significantly reduced with age, but was found to be unchanged in the muscle and the fat (n = 10 young and 10 old mice, P < 0.05). (f) Fasting and fed insulin levels were found to be significantly elevated with age in C57Bl6 mice (n = 6 young and 5 old mice, P < 0.05). (g) C‐peptide levels were found to be significantly elevated with age in the fed state (n = 4 young and 5 old mice, P = 0.02) and (h) Glucagon levels were found to be suppressed in the fasting state in old mice (n = 6 young and 6 old mice, P = 0.02).