The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

Abstract

The continuous delivery of glucose to the brain is critically important to the maintenance of normal metabolic function. However, elucidation of the hormonal regulation of in vivo cerebral glucose metabolism in humans has been limited by the lack of direct, noninvasive methods with which to measure brain glucose. In this study, we sought to directly examine the effect of insulin on glucose concentrations and rates of glucose transport/metabolism in human brain using 1 H-magnetic resonance spectroscopy at 4 Tesla. Seven subjects participated in paired hyperglycemic (16.3 ؎ 0.3 mmol/l) clamp studies performed with and without insulin. Brain glucose remained constant throughout (5.3 ؎ 0.3 mol/g wet wt when serum insulin ‫؍‬ 16 ؎ 7 pmol/l vs. 5.5 ؎ 0.3 mol/g wet wt when serum insulin ‫؍‬ 668 ؎ 81 pmol/l, P ‫؍‬ NS). Glucose concentrations in gray matter-rich occipital cortex and white matter-rich periventricular tissue were then simultaneously measured in clamps, where plasma glucose ranged from 4.4 to 24.5 mmol/l and insulin was infused at 0.5 mU ⅐ kg -1 ⅐ min -1 . The relationship between plasma and brain glucose was linear in both regions. Reversible Michaelis-Menten kinetics fit these data best, and no differences were found in the kinetic constants calculated for each region. These data support the hypothesis that the majority of cerebral glucose uptake/metabolism is an insulin-independent process in humans. Diabetes 50: [2203][2204][2205][2206][2207][2208][2209] 2001 T he brain relies on the continuous delivery of glucose via the blood to maintain normal metabolic function. How glucose delivery into the central nervous system is regulated and how that delivery is altered by different metabolic conditions in the living human have been difficult to ascertain. In particular, the role of insulin in the regulation of cerebral glucose metabolism has been difficult to directly assess. Although evidence acquired using both in vitro and in vivo approaches support and refute the hypothesis that insulin regulates the entry of glucose into brain tissue (1-9), studies performed in living animals have been limited by their inability to directly measure cerebral glucose concentrations.The brain is composed of both gray and white matter. Both rely on glucose for the maintenance of normal function, but the rates at which they metabolize glucose have been found to be different (9,10). Whether these differences in glucose metabolism equate to differences in cerebral glucose concentrations and whether insulin differentially regulates regional cerebral glucose metabolism have not been directly examined in humans because, until recently, direct methods to measure brain glucose concentrations in healthy subjects have not been feasible. Invasive methods to measure intracerebral glucose concentrations, such as the use of an implanted equilibrium dialysis probe, have been reported in abstract form (11), but such a technique is not acceptable in the study of normal human physiology. Indirect methods to quantitate brain glucose concent...

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