Biology Reference
In-Depth Information
Muscle cell
Hexokinase
Glucose
transport
Glycogen
synthase
V
HK
V
GT
Glucose
ex
Glucose
in
Glycogen
G6P
V
-GT
V
glycolysis
Figure 1
Diagram of potential impaired steps in insulin-stimulated muscle glycogen
synthesis in type 2 diabetes.
G6P, glucose-6-phosphate; glucose
ex
, extracellular glucose; glucose
in
, intracellular glucose;
V
glycolysis
, net velocity of the glycolytic flux of glucose-6-phosphate; V
GT
, velocity of glucose
transport into the muscle cell; V
−
GT
, velocity of glucose transport out of the muscle cell; V
HK
,
velocity of glucose phosphorylation of hexokinase. (Reprinted from
Metabolomics by
In Vivo
NMR
(eds Shulman RG and Rothman DL) copyright Wiley, England, 2005.)
and
13
C enrichments were monitored every few minutes in blood samples. The
flux of glycogen synthesis was calculated by measuring the rate of
13
C glucose
accumulating in a selected volume of the gastrocnemius muscle, and the label
flow was converted to mass flow from the substrate enrichment. The validity of
the measurement had been established by previous
in vivo
and
in vitro
13
C MRS
studies. The MRS accuracy was higher than in the previous method of muscle
biopsies and was therefore able to provide meaningful values of the fluxes.
The concentrations of two metabolites in the pathway were also measured
in MRS experiments. The intramuscular concentration of glucose was mea-
sured by
13
C MRS showing that it was very low. Hence, flow through the
glucose transporters was essentially unidirectional and linear with glucose
concentration.
From the experimental measurements of flux the elasticity (as defined in
MCA) of this step with respect to glucose was unity. The responsivity of the flux
to glucose was measured, under insulin clamp, by increasing glucose concentra-
tions and measuring flux changes. The responsivity of flux changes to glucose
changes was also unity. As responsivity equals the product of elasticity and flux
