Sains Malaysiana 39(2)(2010): 315–320
Hydrogen Peroxide Stimulates
Glucose Uptake in Myotube Cells via the Insulin Signaling Pathway
(Hidrogen
Peroksida Merangsang Pengambilan Glukosa ke dalam Sel Miotiub Melalui
Tapakjalan Pengisyaratan Insulin)
Musalmah Mazlan*, Rehanna Mansor & Wan Zurinah Wan Ngah
Department Of Biochemistry, Medical
Faculty, Universiti Kebangsaan Malaysia
Jalan Raja Muda Abdul Aziz, 50300
Kuala Lumpur, Malaysia
Diserahakan: 28 April 2009 / Diterima:
20 Ogos 2009
ABSTRACT
Recent
studies suggest that reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) may exert
beneficial effects on health. Therefore this study evaluated the effects of H2O2 and
gamma-tocotrienol (GTT), an
antioxidant, on D-[2-3H]Glucose
uptake by myotubes compared to insulin. Results showed that H2O2 and insulin
significantly increased D-[2-3H]Glucose
uptake. This was associated with an increased in Vmax but Michaelis constant
(Km) of the transport system remained unchanged indicating that an increase in
amount, rather than affinity, of the glucose transporter was involved in the
process. Western blot studies confirmed that H2O2 increased
the expressions of insulin sensitive glucose transporter, GLUT4 and also hexokinase (an enzyme which phosphorylates glucose
and indirectly stimulates glucose uptake by cells). H2O2 and insulin
also stimulated increased in PPAR-γ
and IRS-1, which are proteins of the
insulin transduction pathway. The present data however showed that GTT did not exert any effect on glucose uptake. Thus, the study
showed that H2O2 mimicked insulin action in stimulating glucose uptake in myotube
cells by influencing the insulin signaling pathway.
Keywords:
Hydrogen peroxide; gamma-tocotrienol; glucose uptake; insulin action; myotube
cells
ABSTRAK
Kajian-kajian
terkini mencadangkan bahawa spesies oksigen reaktif (ROS) seperti hidrogen peroksida (H2O2) boleh
memberi kesan berguna ke atas kesihatan. Oleh itu kajian ini menilai kesan H2O2 and
gama-tokotrienol (GTT), suatu
antioksidan, ke atas pengambilan D-[2-3H]Glukosa oleh sel miotiub berbanding insulin. Keputusan
menunjukkan bahawa H2O2 and insulin meningkatkan pengambilan D-[2-3H]Glukosa secara signifikan. Peningkatan ini berkaitan dengan
peningkatan Vmaks tetapi pemalar Michaelis (Km) sistem pengangkutan tidak
berubah yang menunjukkan bahawa peningkatan bilangan dan bukannya peningkatan
afiniti pengangkut glukosa yang terlibat dalam proses ini. Kajian blot Western
mengesahkan yang H2O2 meningkatkan ekspresi pengangkut glukosa peka insulin, GLUT4 dan juga heksokinase (enzim yang memfosforilasi glukosa dan
secara taklangsung merangsang pengambilan glukosa oleh sel). H2O2 dan insulin
juga merangsang peningkatan PPAR-γ
dan IRS-1, iaitu protein-protein
dalam tapakjalan transduksi insulin. Data daripada kajian ini walau
bagaimanapun, menunjukkan bahawa GTT tidak memberi kesan ke atas pengambilan glukosa oleh sel. Oleh
itu, kajian ini menunjukkan bahawa H2O2 bertindak
seperti insulin dalam merangsang pengambilan glukosa oleh sel miotiub dengan mempengaruhi
tapakjalan pengisyaratan insulin.
Kata kunci:
Gama-tokotrienol; hidrogen peroksida; pengambilan glukosa; sel miotiub;
tindakan insulin
RUJUKAN
Al Shamsi, M.S., Amin, A. & Adeghate, E. 2004. Beneficial
effect of vitamin E on the metabolic parameters of diabetic rats. J Mol Cell
Bioch. 261: 35-42.
Barbagallo, M., Dominguez, L.J., Tagliamonte, M.R., Resnick,
L.M. & Paolisso, G. 1999. Effects of vitamin E and glutathione on glucose
metabolism. Hypertension 34: 1002-1006.
Birnbaum, M. J. 1992. The insulin-sensitive glucose transporter. Int. Rev. Cytol. 137A: 239 -297.
Caballero, B. 1993. Vitamin E improves action of insulin. Nutr
Rev. 51: 339-340.
Droege, W. (2001) Free radicals in the physiological control of
cell function. Physiol. Rev. 82: 47-95.
Frevert, E.U. & Kahn, B.B. 1997. Differential effects of
constitutively active phosphotidylinositol 3-kinase on glucose transport,
glycogen synthase activity and DNA synthesis in 3T3-L1 adipocytes. Mol Cell
Biol. 17: 190-198.
Ge, X., Yu,
Q., Qi,W., Shi, X. & Zhai, Q. 2008. Chronic insulin treatment causes
insulinresistance in 3T3-L1 adipocytes through oxidative stress. Free Radic.
Res. 42(6): 582-591.
Groeger, G., Quiney, C. & Cotter, T.G. 2009. Hydrogen
peroxide as a cell survival signaling molecule. Antioxid Redox Signal,
26 [Epub].
Ha, H. & Lee, H.B. 2000. Reactive oxygen species as glucose
signaling molecules in mesangial cells cultured and under high glucose. Kidney
Int. Suppl. 77: S19-S25.
Hansen, P., Gulve, E., Gao, J., Schluter, J., Mueckler, M. &
Holloszy, J. 1995. Kinetics of 2-deoxyglucose transport in skeletal muscle:
effects of insulin and contractions. Am. J. Physiol. 268: C30 – C35.
Heffer, D., Rutter, W.J. & Zick, Y. 1992. The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine
phosphorylation of potential target protein for the insulin receptor kinase in
intact cells. J. Bioch. 288: 631-635.
Kamal-Edlin, A. & Appelqist, L.A. 1996. The chemistry and
antioxidant properties of tocopherols and tocotrienols. Lipids. 31:
671-701.
Mandarino, L.J., Printz, R.L. & Cusi, K.A. 1995. Regulation
of hexokinase II and glycogen synthase mRNA, protein and activity in human
muscle. Am. J. Physiol. 269: 707-708.
Moorthi, R.V., Bobby, Z., Selvaraj, N. & Sridhar, M.G. 2006.
Vitamin E protects the insulin sensitivity and redox balance in rat L6 muscle
cells exposed to oxidative stress. Clin. Chim. Acta. 367: 132-136.
Nindl, G. 2004. Hydrogen peroxide – from oxidative stressor to
redox regulator. Cellscience 1(2): 1-10.
Paolisso, G., D’Amore, A. & Volpe, C. 1994. Evidence for a
relationship between oxidative stress and insulin action in non-insulin
dependent (type II) diabetic patients. Metab. 43: 1426-1429.
Printz, R.L., Koch, S., Potter, L.R., O’Doherty, R.M., Tiosinga,
J.J., Moritz, S. & Granner, D.R. 1993. Hexokinase II mRNA and gene
structure, regulation by insulin and evolution. J. Biol. Chem. 268:
5209-5219.
Rudich, A., Tirosh, A., Potashnik, R., Herni, R., Kanety, H.
& Bashan, N. 1998. Prolonged oxidative stress impairs insulin-induced GLUT4
translocation in 3T3-L1 adipocytes. Diabetes 47(10): 1562-1569.
Shepherd, P.R., Withers, D.J. & Siddle, K. 1998.
Phosphoinositide 3-kinase: the key switch mechanism in insulin signaling. Bioch.
J. 333: 471-490.
Yannan, H., Tatsuo, I., Atsushi, M., Kazuo, K., Masayoshi, I.,
Mika, K. Yoritsuna, Y, Yasunori, K., Hiroyuki, M., Yoshihiro, U. & Keigo, Y. 2002. Effect of 1, 25-dihydroxyvitamin D3 and vitamin E on
insulin-induced glucose uptake in ratadipocytes. Diabetes Res Clin Pract.
55: 175-183.
*Pengarang untuk surat-menyurat; email: musalmah@medic.ukm.my