No effect of insulin on glucose blood-brain barrier transport and cerebralmetabolism in humans

The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transpo rt and cerebral metabolism (CMRglc) was studied using the intravenous doubl e-indicator method and positron emission tomography using [F-18]fluorodeoxy glucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/ - 4 years old) mere studied twice during a euglycemic and a euglycemic-hype rinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose. Duri ng insulin infusion, arterial plasma insulin levels increased from 48.5 to 499.4 pmol/l. The permeability-surface area products for glucose and FDG BB B transport obtained with the double-indicator method remained constant dur ing hyperinsulinemia. Similarly using PET-FDG, no changes mere observed in the unidirectional clearance of FDG from blood to brain. k(2)* (FDG transpo rt from brain to blood) increased significantly by 15 and 18% (gray and whi te matter, respectively), and k(4)* (dephosphorylation of FDG) increased by 18%. The increase in k(2)* may be caused by insulin inducing a decrease in the available FDG brain pool, The increase in k(2)* may be related to an i ncreased loss of labeled products during insulin fusion. Irrespective of th ese changes, CMRglc remained unchanged in all brain regions. We conclude th at hyperinsulinemia within the normal physiologic range does not affect BBB glucose transport or net cerebral glucose metabolism.