Download Abstract - Creighton University

“Biochemical Studies on Uncoupling
Publications:



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Strommer, L.; Abou El-Ella, G.; Kamel, A.; Marcus, C.;
Hager, P.; Adrian, T. E.; Permert J, 2001 “Upregulation of
uncoupling protein homologues in skeletal muscle but not
adipose tissue in posttraumatic insulin resistance” J.Biochem
Biophys Res Commun 281,(2),334-40.
Abou El-Ella G, Isaksson B, Permert J, Adrian, T.E.
Increased expression of uncoupling proteins 2 and 3 in insulinresistant muscle from pancreatic cancer patients (submitted to
Journal of Clinical Endocrinology and Metabolism).
Abou EL-Ella G, Adrian TE. Up-regulation of uncoupling
proteins by Tumor necrosis factor- (TNF-) and IL-1 in Glut4 transfected L6. (in preparation)
Abou EL-Ella G, Adrian TE. Modulation of TNF--induced
expression
of
uncoupling
protein-3
through
the
sphingomyelinase pathway in myotubes (in preparation)
Proteins and Glucose Metabolism in
Skeletal Muscle”
Doctoral Thesis Defense
by
Ghada Abou El-Ella
Major Advisor
Dr. Thomas Adrian
Oral presentations and Seminars:

Internal Advisor
Oral presentation at the Midwest Student Biomedical
Dr. Richard F. Murphy
Research Forum , Omaha NE 2001 “Uncoupling protein 2 and
Graduate Committee
3 expression in skeletal muscle is significantly increase in posttrumatic rats”

Dr. Naser Alsharif
Dr. Terence Lawson
Seminar to the Biomedical Science Dept., Creighton
university 2001 “Uncoupling proteins and cachexia”

Dr. Alan Richards
Dr. Jack Yee
Oral presentation at the Annual Meeting of the American
Pancreatic Association, Chicago November, 2001 “Marked
increase in skeletal muscle uncoupling protein 2 and 3
expression in pancreatic cancer”

Friday, December 13, 2002
3 pm
Room B 58
Creighton University
Oral presentation at the Midwest student Biomedical
research Forum, Omaha NE 2002 “Uncoupling protein 2 and 3
expression in skeletal muscle is markedly increased in
pancreatic cancer”
Abstract
Department of Biomedical Sciences
Uncoupling protein (UCP) is an inner-mitochondrial membrane
protein that uncouples the production of ATP from the electron transport
chain, thereby inducing thermogenesis. Recently, a family of UCP
homologues was identified, two of which (UCP-2 and UCP-3) are highly
expressed in skeletal muscle. The physiological function of these
UCPs is not established, but evidence suggests that they are
involved in the regulation of metabolism rather than
thermogenesis.
The aim of my project was to investigate the relationship
between uncoupling protein expression and alterations in glucose
metabolism in different pathological conditions. In the first part of
these studies, the expression of uncoupling proteins in pancreatic
cancer patients was determined. A significant increase in UCP-3
and UCP-2 protein and mRNA expression was detected. This
increase was associated with impaired insulin response and
decreased ATP and phosphocreatine contents, indicating loss of
energy. To further explore the relationship between UCP and
insulin resistance, expression of the UCPs and glucose
metabolism was examined in skeletal muscle samples from a
post-traumatic rat model. A significant increase of UCP-2 and
UCP-3 expression was observed, indicating a strong relationship
between UCP expression and alterations in glucose metabolism
and substrate utilization.
The reported involvement of TNF- and IL-1 in the
pathogenesis of cachexia and insulin resistance triggered
investigation of the effect of these inflammatory cytokines on the
expression of the UCPs in skeletal muscle cells. TNF- and IL-1
induced an increase in the expression of UCP-2 and UCP-3 that
was positively associated with an increase in glucose uptake in
Glut-4 transfected L6 myotubes. These findings relate increased
glucose uptake to an increase in UCP expression. Finally, the
signal pathway through which TNF- induces its effect was
investigated. The results of this study show that TNF- stimulates
an increase in UCP expression and glucose uptake through a
SMase-ceramide-dependant pathway which includes activation of
MAPK and translocation of NF-B to the nucleus.
Experiments were then designed to try to uncover whether
uncoupling caused an increase in glucose uptake or vice versa.
Treatment of Glut-4 transfected L6 myotubes with the uncoupling
agent, dinitrophenol resulted in an increase in glucose uptake,
which was presumably a response to mitochondrial uncoupling.
The glucose analogue, 2-deoxyglose is taken up into cells and
phosphorylated but is not further metabolized. When 80% of the
glucose in the media was replaced with 2-deoxyglucose, the
stimulatory effect of TNF- on the UCP expression was abolished,
suggesting that the increase in UCP expression is dependent on
the increase in glucose uptake. Taken together, these results
support our hypothesis that there is a close relationship between
an increase in UCP expression and glucose uptake. However,
one study shows that glucose uptake increases in response to
mitochondrial uncoupling, while the other shows that, when the TNF-
stimulated increase in glucose uptake is prevented this, in turn, prevents
the increase of UCP expression. Thus, a question still remains as to
whether increased glucose uptake induces UCP expression or the
reverse pertains.
Acknowledgements:
This work was supported by funds from the Egyptian government, the NCI
SPORE program, the Lustgarten Foundation for Pancreatic Cancer
Research and the American Institute for Cancer Research.
Biography:
 Born in Assiut Egypt
 Bachelors Degree in Veterinary Medical Sciences (BVMSc)
(1991): Assiut University, Egypt – grade: Very Good with Honors.
 Masters degree of Veterinary Science (MVSc) in Biochemistry
(1996): Tanta University, Egypt "Effect of Flunixin meglumine
(Finadyne) on carbohydrate metabolism and liver function in
female rats"
Position:
 Demonstrator, Biochemistry Department, school of Veterinary
Medicine, Tanta University (1992-1996)
 Assistant Lecturer, Biochemistry Department, School of
Veterinary Medicine, Tanta University 1996-1997
 Assistant Lecturer, Biochemistry Department, School of
Veterinary Medicine, South Valley University 1997-1999
 Ph.D. candidate, 1999-present, Department of Biomedical
Sciences, Creighton University