Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat

We examined the hypothesis that the uptake of plasma insulin into cerebrospinal fluid (CSF) is saturable in two rat models. Dietary obese and control female Osborne Mendel rats received 24-h infusions of vehicle or insulin. CSF insulin levels in cafeteria- and chow-fed rats were comparable at all levels of plasma insulin (4.5 ± 2.8, 7.6 ± 2.4, and 23.9 ± 6.4 μU/ml in cafeteria diet vs. 4.5 ± 0.9, 6.8 ± 1.1, and 17.0 ± 4.0 μU/ ml in chow rats). CSF insulin uptake as a percentage of plasma insulin decreased with increased plasma insulin in both groups. A similar relationship was observed in Wistar rats receiving 6-day infusions of vehicle or insulin (plasma insulin = 55 ± 12 vs. 365 ± 98 μU/ml; CSF/plasma insulin ratio = 0 ± .007 vs. 0.013 ± .006, respectively). Hyperinsulinemic Wistar rats did not demonstrate decreased brain capillary insulin binding vs. vehicle-infused controls. The results suggest that a saturable transport process contributes insulin transport into CSF in normal rats and that this process is not altered by moderate diet-induced obesity or hyperinsulinemia per se.