TY - JOUR

T1 - No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans

AU - Hasselbalch, S G

AU - Knudsen, G M

AU - Videbaek, C

AU - Pinborg, L H

AU - Schmidt, Jes F

AU - Holm, Søren

AU - Paulson, O B

PY - 1999/10

Y1 - 1999/10

N2 - The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transport and cerebral metabolism (CMRglc) was studied using the intravenous double-indicator method and positron emission tomography using [18F]fluorodeoxyglucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/- 4 years old) were studied twice during a euglycemic and a euglycemic-hyperinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose. During insulin infusion, arterial plasma insulin levels increased from 48.5 to 499.4 pmol/l. The permeability-surface area products for glucose and FDG BBB transport obtained with the double-indicator method remained constant during hyperinsulinemia. Similarly using PET-FDG, no changes were observed in the unidirectional clearance of FDG from blood to brain. k2* (FDG transport from brain to blood) increased significantly by 15 and 18% (gray and white matter, respectively), and k4* (dephosphorylation of FDG) increased by 18%. The increase in k2* may be caused by insulin inducing a decrease in the available FDG brain pool. The increase in k4* may be related to an increased loss of labeled products during insulin fusion. Irrespective of these changes, CMRglc remained unchanged in all brain regions. We conclude that hyperinsulinemia within the normal physiologic range does not affect BBB glucose transport or net cerebral glucose metabolism.

AB - The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transport and cerebral metabolism (CMRglc) was studied using the intravenous double-indicator method and positron emission tomography using [18F]fluorodeoxyglucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/- 4 years old) were studied twice during a euglycemic and a euglycemic-hyperinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose. During insulin infusion, arterial plasma insulin levels increased from 48.5 to 499.4 pmol/l. The permeability-surface area products for glucose and FDG BBB transport obtained with the double-indicator method remained constant during hyperinsulinemia. Similarly using PET-FDG, no changes were observed in the unidirectional clearance of FDG from blood to brain. k2* (FDG transport from brain to blood) increased significantly by 15 and 18% (gray and white matter, respectively), and k4* (dephosphorylation of FDG) increased by 18%. The increase in k2* may be caused by insulin inducing a decrease in the available FDG brain pool. The increase in k4* may be related to an increased loss of labeled products during insulin fusion. Irrespective of these changes, CMRglc remained unchanged in all brain regions. We conclude that hyperinsulinemia within the normal physiologic range does not affect BBB glucose transport or net cerebral glucose metabolism.

KW - Adult

KW - Biological Transport, Active

KW - Blood Glucose/metabolism

KW - Blood-Brain Barrier/physiology

KW - Brain/metabolism

KW - Fluorodeoxyglucose F18/pharmacokinetics

KW - Humans

KW - Insulin/blood

KW - Permeability

KW - Radiopharmaceuticals/pharmacokinetics

KW - Reference Values

KW - Tissue Distribution

KW - Tomography, Emission-Computed

U2 - 10.2337/diabetes.48.10.1915

DO - 10.2337/diabetes.48.10.1915

M3 - Journal article

C2 - 10512354

VL - 48

SP - 1915

EP - 1921

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -