Western blot results showed that, streptozotocin induced diabetic mice has significantly downregulated level of GLUT4 protein in both cytosol and membrane faction. However, membrane to cytosol ratio (m/c) was not significantly decreased.
Please read some of the recent review articles concerning the cis- and trans-acting regulatory factors involved in Glut4 gene expression for a better understanding. While insulin alone causes translocation of Glut4 from intracellular to cell-membrane in the short-run, that represents only half of the overall picture.
It's is used in rats to obtein cancer more quickly in lab, this normally produce DM in rats.
I think your animals' diet play major role on Glut4 gene expression. L-glutamine and L-serine may be effective.
Mol Cell Biol. 2001 Nov;21(22):7852-61.
Activation of protein kinase C zeta induces serine phosphorylation of VAMP2 in the GLUT4 compartment and increases glucose transport in skeletal muscle.
Braiman L1, Alt A, Kuroki T, Ohba M, Bak A, Tennenbaum T, Sampson SR.
L-glutamine supplementation induces insulin resistance
in adipose tissue and improves insulin signalling in liver
and muscle of rats with diet-induced obesity
P. O. Prada & S. M. Hirabara & C. T. de Souza &
A. A. Schenka & H. G. Zecchin & J. Vassallo &
L. A. Velloso & E. Carneiro & J. B. C. Carvalheira &
R. Curi & M. J. Saad
Received: 19 March 2007 /Accepted: 30 April 2007 / Published online: 29 June 2007
# Springer-Verlag 2007
Abstract
Aims/hypothesis Diet-induced obesity (DIO) is associated
with insulin resistance in liver and muscle, but not in
adipose tissue. Mice with fat-specific disruption of the gene
encoding the insulin receptor are protected against DIO and
glucose intolerance. In cell culture, glutamine induces
insulin resistance in adipocytes, but has no effect in muscle
cells. We investigated whether supplementation of a highfat
diet with glutamine induces insulin resistance in adipose
tissue in the rat, improving insulin sensitivity in the whole
animal.
Materials and methods Male Wistar rats received standard
rodent chow or a high-fat diet (HF) or an HF supplemented
with alanine or glutamine (HFGln) for 2 months. Light
microscopy and morphometry, oxygen consumption, hyperinsulinaemic–euglycaemic
clamp and immunoprecipitation/
immunoblotting were performed.
Results HFGln rats showed reductions in adipose mass and
adipocyte size, a decrease in the activity of the insulininduced
IRS–phosphatidylinositol 3-kinase (PI3-K)–protein
kinase B–forkhead transcription factor box 01 pathway in
adipose tissue, and an increase in adiponectin levels. These
results were associated with increases in insulin-stimulated
glucose uptake in skeletal muscle and insulin-induced
suppression of hepatic glucose output, and were accompanied
by an increase in the activity of the insulin-induced
IRS–PI3-K–Akt pathway in these tissues. In parallel, there
were decreases in TNFα and IL-6 levels and reductions in
c-jun N-terminal kinase (JNK), IκB kinase subunit β
(IKKβ) and mammalian target of rapamycin (mTOR)
activity in the liver, muscle and adipose tissue. There was
also an increase in oxygen consumption and a decrease in
the respiratory exchange rate in HFGln rats.
Conclusions/interpretation Glutamine supplementation
induces insulin resistance in adipose tissue, and this is
accompanied by an increase in the activity of the hexosamine
pathway. It also reduces adipose mass, consequently attenuating
insulin resistance and activation of JNK and IKKβ,
while improving insulin signalling in liver and muscle.
Keywords Akt . Glutamine . High-fat diet .
Insulin resistance . Insulin signalling .
Phosphatidylinositol 3-kinase . Obesity . PI-3K
D
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