In
type 2 Diabetes, oxidative stress plays an important role in development and aggregation of
insulin resistance. In the present study, long term administration of the
dexamethasone led to the development of
insulin resistance in mice. The effect of
thiazolidinediones pioglitazone and
rosiglitazone, with
melatonin on
dexamethasone-induced
insulin resistance was evaluated in mice.
Insulin resistant mice were treated with combination of
pioglitazone (10 mg/kg/day, p.o.) or
rosiglitazone (5 mg/kg/day, p.o.) with
melatonin 10 mg/kg/day p.o. from day 7 to day 22. In the biochemical parameters, the serum
glucose,
triglyceride levels were significantly lowered (P<0.05) in the combination groups as compared to
dexamethasone treated group as well as with individual groups of
pioglitazone,
rosiglitazone, and
melatonin. There was also, significant increased (P<0.05) in the
body weight gain in combination treated groups as compared to
dexamethasone as well as individual groups. The combination groups proved to be effective in normalizing the levels of
superoxide dismutase,
catalase,
glutathione reductase and lipid peroxidation in liver homogenates may be due to
antioxidant effects of
melatonin and decreased
hyperglycemia induced
insulin resistance by
thiazolidinediones. The
glucose uptake in the isolated hemidiaphragm of mice was significantly increased in combination treated groups (PM and RM) than
dexamethasone alone treated mice as well as individual (
pioglitazone,
rosiglitazone,
melatonin) treated groups probably via increased in expression of GLUT-4 by
melatonin and
thiazolidinediones as well as increased in
insulin sensitivity by
thiazolidinediones. Hence, it can be concluded that combination of
pioglitazone and
rosiglitazone,
thiazolidinediones, with
melatonin may reduces the
insulin resistance via decreased in oxidative stress and control on
hyperglycemia.