الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Type 2 diabetes mellitus (T2DM) is a group of metabolic disorders manifested by
hyperglycemia as a result of insulin insufficiency and/or resistance. Insulin resistance is the
inability of insulin to exert its action on cells. The pathophysiology of T2DM is not fully
understood and there are theories link T2DM with insulin signaling defects and obesity.
The increasing prevalence of T2DM has stimulated the development of many new
approaches to safely treat hyperglycemia. The main goal of these therapies is to maintain
near-normal glucose levels, and therefore prevent the development of diabetes
complications.
Adipose tissues play an important role in the development of insulin resistance and
T2DM. There are two kinds of adipose tissue: white adipose tissue (WAT) and brown
adipose tissue (BAT). WAT is the primary site of energy storage in the form of
triglycerides, whereas BAT plays a substantial role in non-shivering thermogenesis. The
treatment based on diet and life style modifications with administration of oral
hypoglycemic agents or insulin which may be helpful in some cases. The most used oral
hypoglycemic agent is metformin, which enhances the muscle glucose uptake, increases
insulin signaling so, improves the islet cells responsiveness to glucose.
Scientists identified a novel co-regulator (SERTAD2), which regulates adipocyte
biology and energy metabolism. Its expression in adipose tissue is necessary for the
development of diet- and age-induced obesity. Also, UCP2 that is expressed in the adipose
tissues is suggested to have a role in the pathogenesis of T2DM and insulin resistance
through the control of the mitochondrial functions because mitochondria are the main sites
for energy metabolism.
The aim of our study is to evaluate the expression of SERTAD2 and UCP2 genes in
the white and brown adipose tissues in STZ-induced type 2 diabetic rats and investigate the
possible effects of metformin treatment on glucose homeostasis, lipid profile and gene
expression of SERTAD2 and UCP2 genes. Fifty rats divided into three groups; ten normal
rats fed with standard diet, ten HFD/STZ-induced diabetic rats without treatment and the
remaining thirty rats subdivided into three HFD/STZ-induced diabetic groups treated with
three different doses of metformin (100, 200 and 300 mg/kg/day) for 4 weeks; ten rats for
each dose.
The diabetic rats showed hyperglycemia, insulin resistance and dyslipidemia. The
treatment with metformin results in dose-dependent decline in glucose homeostasis
parameters and lipid profile parameters except the HDL-C level which showed higher
levels for the treated rats than the untreated ones. The expression of SERTAD2 gene
showed up regulation in the WAT and BAT of untreated diabetic rats, while the treated rats
showed down regulation of the SERTAD2 gene expression in a dose dependent manner.
On the other hand, the UCP2 gene expression was down-regulated in WAT and BAT of the
Summary and Conclusion
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untreated rats and the treatment with metformin results dose-dependent up-regulation of its
expression.
from the results of our study and other related studies, we can conclude that:
1. The HFD/STZ model, characterized by overt hyperglycemia, dyslipidemia,
hyperinsulinemia, and insulin resistance, that would closely reflect the
metabolic characteristics of T2DM, and it could be used for pharmacological
testing.
2. The diabetic rats showed excessive up-regulation of SERTAD2 gene expression
in both types of adipose tissues (WAT and BAT) which associated with downregulation
of UCP2.
3. Treatment of diabetic rats with metformin significantly and dose-dependently
ameliorates the expression of SETAD2 and UCP2 in adipose tissues.
4. The amelioration of SERTAD2 and UCP2 expressions are correlated with the
correction of glucose homeostasis parameters and lipid profile.
5. These results indicated that SERTAD2 and UCP2 in adipose tissues could be
the molecular targets of metformin.