Kinetics and specificity of insulin uptake from plasma into cerebrospinal fluid
Schwartz, M.W.; Sipols, A.; Kahn, S.E.; Lattemann, D.F.; Taborsky, G.J.; Bergman, R.N.; Woods, S.C.; Porte, D.
American Journal of Physiology 259(3 Pt 1): E378-E383
1990
ISSN/ISBN: 0002-9513 PMID: 2205107 Document Number: 352845
To characterize the relationship between insulin levels in plasma and those in cerebrospinal fluid (CSF), we studied the kinetics of both the uptake of insulin into CSF from plasma and the turnover of insulin within the CSF compartment. Sustained physiological levels of euglycenic hyperinsulinemia (plasma insulin .apprx. 500 pM) did not alter CSF insulin levels within the 1st h, but by 90 min a significant increase was observed (P < 0.01). During graded hyperinsulinemic clamps (mean plasma insulin .apprx. 500-15,000 pM), CSF insulin rose in a dose-depndent fashion. This rise was characterized by an initial delay followed by a continuous increase for the next 150 min. We also found that after brief, high-dose intravenous insulin infusions, the T1/2 of CSF insulin was 143 .+-. 7 min (mean .+-. SE; n = 4), similar to that of CSF turnover by bulk flow. To test the specificity of CSF insulin uptake from plasma, we compared this uptake during intravenous insulin infusions with that of proinsulin, a peptide with reduced affinity for the insulin receptor. We observed a significantly lower increment of CSF proinsulin levels over 180 min (13.6 .+-. 1.6 pM; means .+-. SE; n = 4) compared with that of insulin (22.4 .+-. 0.6 pM; n = 4; P < 0.01), despite plasma proinsulin levels higher than insulin (1,890 .+-. 287 vs. 1,283 .+-. 192 pM; P < 0.001). When corrected for the difference in plasma levels, the uptake of insulin was fivefold greater than that of proinsulin. Taken together, these observations indicate that, despite an initial delay, physiological increases in plasma insulin produce significant elevations of CSF insulin levels and are consistent with the hypothesis that insulin uptake into CSF occurs in part via a mechanism with specificity for insulin.