The rate of glucose uptake over the blood-brain barrier in humans in vivo, measured by 13C magnetic resonance spectroscopy

Glucose is the principal source of energy for normal brain function. The brain
accounts for more than half the body's glucose use. Since the brain*s capacity
to store glucose as glycogen is limited, a continuous supply of glucose from
the circulation is mandatory. Glucose is transported across the blood-brain
barrier into the brain through glucose transporter-1 (GLUT-1) and directly into
neurons at places where the blood-brain barrier is absent through GLUT-3. Both
glucose transporters mediate facilitative energy-independent transport, so that
glucose is taken up by brain tissue relatively unimpeded.
The rate of glucose transport into the brain depends on the concentration of
transporter proteins, the concentration difference between intra- and
extracellular glucose levels and the metabolism of glucose. Several models have
been devised that describe the flow of glucose from blood to brain and within
different brain cells under basal and hyperglycaemic steady-state conditions.
However, little is known about the rate of cerebral glucose uptake under in
vivo non-steady state-conditions, e.g. after glucose loading. It is similarly
unknown whether patients with type 1 diabetes behave differently than
non-diabetic subjects. Such knowledge is especially relevant with respect to
the recent clinical introduction of real-time glucose sensors in the management
of (type 1) diabetes. Real-time glucose sensors measure glucose levels
semi-continuously in the interstitial fluid, but do so at an estimated lag time
relative to blood of 4-10 minutes (1) or greater (2).
13C Magnetic Resonance Spectroscopy (MRS) of the brain provides a unique tool
to investigate the dynamics of cerebral glucose uptake in humans in vivo. We
recently developed a protocol to investigate the effects of steady-state normo-
and hypoglycaemia on brain glucose uptake and subsequent metabolism in humans
in vivo (3). In this protocol, a 30 ml bolus of 100% 13C labelled
([1-13C]glucose) 20% w/w glucose solution is infused over 10 minutes to rapidly
increase plasma 13C enrichment. Peak values of 13C labelled glucose in the
brain appeared to lag 5-10 minutes behind peak plasma glucose levels. However,
since glucose was measured every 5 minutes, the lag time could not be measured
more precisely. The objective of the current research project is to accurately
assess the time difference between blood glucose and cerebral glucose using 13C
MRS in response to immediate, transient hyperglycaemia.

To investigate the time difference between the blood glucose excursion and the
subsequent appearance of cerebral 13C glucose after intravenous glucose
loading.

Interventional study to investigate the rate of glucose uptake in the brain by
MR spectroscopy and [1-13C]glucose infusion.

Volunteers receive a bolus of [1-13C]glucose intravenously. During an hour
blood will be sampled from an arterial line to determine plasma glucose values
and in the brain glucose uptake is measured by 13C MR spectroscopy. Diabetic
patients who participate receive a standardized dose of insulin.

Administration of [1-13C] glucose
Blood sampling through arterial line
Insulin administration in patients

Burden:
Time investment
Staying sober
Arterial and venous lines
MR scan

Risks:
Findings on cerebral MR scan
Hematoma due to intraarterial and intravenous cannulations
Phlebitis due to IV glucose infusion
Claustrophobia in MR scanner