TY - JOUR

T1 - High dose insulin does not increase glucose transfer across the blood-brain barrier in humans

T2 - a re-evaluation

AU - Knudsen, G M

AU - Hasselbalch, S G

AU - Hertz, M M

AU - Paulson, O B

PY - 1999/8

Y1 - 1999/8

N2 - BACKGROUND: This study re-evaluates previously published data on blood-brain barrier transfer coefficients in humans exposed to high insulin levels.DESIGN: In this study of seven volunteers, global blood-brain barrier permeability to glucose and phenylalanine was measured by means of the intracarotid double-indicator method before, during, and after an insulin-glucose clamp. Data were reanalyzed by means of a mathematical model that takes capillary heterogeneity and labelled glucose backflux from the brain into account.RESULTS: The permeability-surface area product (PS) for glucose transport from the blood into the brain, PS1, was 0.145 (0.102-0.211) (median and quartiles), 0.146 (0.113-0.259), and 0.157 (0.133-0.181) ml g-1 min-1 before, during, and after insulin challenge, respectively. In six of the subjects, PS for transport from brain to blood over the brain glucose distribution volume, PS2/Ve decreased under hyperinsulinemia, from a baseline value of 6.56 (3.0-14.9) to 3.86 (1.41-5.32), and restored to a value of 3.8 (2.8-12.1) min-1 after insulin challenge. This decrease in PS2/Ve is probably due to an increase in the brain glucose distribution volume induced by an insulin induced increased intracellular glucose uptake during the experiment. For phenylalanine (n = 5), PS1 was unchanged before, during, and after insulin challenge. In hyperinsulinemia, PS3/Ve for phenylalanine decreased in all subjects.CONCLUSION: We conclude that acutely elevated high plasma insulin levels in humans does not alter the brain uptake of glucose or phenylalanine from the blood. It seems, however, that high plasma insulin levels induce an increase in the movement of D-glucose and L-phenylalanine from the brain interstitial fluid into the intracellular compartment.

AB - BACKGROUND: This study re-evaluates previously published data on blood-brain barrier transfer coefficients in humans exposed to high insulin levels.DESIGN: In this study of seven volunteers, global blood-brain barrier permeability to glucose and phenylalanine was measured by means of the intracarotid double-indicator method before, during, and after an insulin-glucose clamp. Data were reanalyzed by means of a mathematical model that takes capillary heterogeneity and labelled glucose backflux from the brain into account.RESULTS: The permeability-surface area product (PS) for glucose transport from the blood into the brain, PS1, was 0.145 (0.102-0.211) (median and quartiles), 0.146 (0.113-0.259), and 0.157 (0.133-0.181) ml g-1 min-1 before, during, and after insulin challenge, respectively. In six of the subjects, PS for transport from brain to blood over the brain glucose distribution volume, PS2/Ve decreased under hyperinsulinemia, from a baseline value of 6.56 (3.0-14.9) to 3.86 (1.41-5.32), and restored to a value of 3.8 (2.8-12.1) min-1 after insulin challenge. This decrease in PS2/Ve is probably due to an increase in the brain glucose distribution volume induced by an insulin induced increased intracellular glucose uptake during the experiment. For phenylalanine (n = 5), PS1 was unchanged before, during, and after insulin challenge. In hyperinsulinemia, PS3/Ve for phenylalanine decreased in all subjects.CONCLUSION: We conclude that acutely elevated high plasma insulin levels in humans does not alter the brain uptake of glucose or phenylalanine from the blood. It seems, however, that high plasma insulin levels induce an increase in the movement of D-glucose and L-phenylalanine from the brain interstitial fluid into the intracellular compartment.

KW - Adolescent

KW - Adult

KW - Biological Transport, Active/drug effects

KW - Blood Glucose/metabolism

KW - Blood-Brain Barrier/drug effects

KW - Glucose/metabolism

KW - Humans

KW - Insulin/administration & dosage

KW - Kinetics

KW - Phenylalanine/blood

U2 - 10.1046/j.1365-2362.1999.00528.x

DO - 10.1046/j.1365-2362.1999.00528.x

M3 - Journal article

C2 - 10457152

VL - 29

SP - 687

EP - 691

JO - European Journal of Clinical Investigation, Supplement

JF - European Journal of Clinical Investigation, Supplement

SN - 0960-135X

IS - 8

ER -