Regional Cerebral Glucose Transport in Insulin-Dependent Diabetic Patients Studied Using [11C]3-O-Methyl-D-Glucose and Positron Emission Tomography

Author:

Brooks D. J.12,Gibbs J. S. R.2,Sharp P.2,Herold S.1,Turton D. R.1,Luthra S. K.1,Kohner E. M.2,Bloom S. R.2,Jones T.1

Affiliation:

1. MRC Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England

2. Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, England

Abstract

Regional cerebral [11C]3- O-methyl-d-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 m M), and four were studied at hyperglycaemic plasma glucose levels (mean 13 m M). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 m M had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and d-glucose for the passive facilitated transport carrier system for hexoses across the blood–brain barrier (BBB). It is concluded that the number and affinity of d-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of d-glucose across the BBB.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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