الفهرس 
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Abstract
The aim of the present investigation was to study the effect of quercetin treatment on glycemic state, insulin resistance & skeletal muscle performance and to elucidate the possible underlying mechanisms of action in experimentally induced type II diabetic male rats.
To achieve this aim 50 adult male albino rats were used. Rats were divided equally into five experimental groups: non-diabetic, diabetic non-treated, diabetic quercetin-treated, diabetic metformin-treated & diabetic combined quercetin and metformin-treated.
By the end of the experimental period (4 weeks), fasting retro-orbital blood samples were collected for estimation of fasting serum glucose, insulin, glycosylated hemoglobin (HbA1C), TNF-α, total antioxidant capacity, MDA & insulin resistance was calculated . Then the rats were sacrificed & hemi-diaphragm was dissected from each rat for recording the strength of muscle contraction at the start and after 30 min activity & the percentage of change in strength of muscle contraction was calculated. Samples from the bathing Krebs solution were taken for estimation of glucose uptake by hemi-diaphragm after 30 min activity and 30 min recovery. After taking the hemi-diaphragm, the gastrocnemius muscle was dissected from its bony attachment & weighed; the tibia was freed from the surrounding tissues & gastrocnemius weight per unit of tibial length (Gast wt/ Tib length ratio) was calculated.
In the present investigation, it was found that fasting serum glucose, glycosylated hemoglobin (HbA1C), insulin, serum TNF-α, MDA level & HOMA-IR index were significantly higher; while the total antioxidant capacity, Gast wt/ Tib L ratio, the strength of muscle contraction at the start and after 30 min activity, the percentage of change -124- Summary
in strength of muscle contraction & glucose uptake by the muscle during 30 min activity and after 30 min recovery were significantly lower in type II diabetic non-treated group when compared to the corresponding values of non-diabetic group.
The diabetic quercetin-treated group revealed statistical significant reduction of fasting serum glucose, glycosylated hemoglobin (HbA1C), TNF-α, MDA level & HOMA-IR index; insignificant change in serum insulin level and statistical significant elevation of total antioxidant capacity, Gast wt/ Tib L ratio, the in-vitro strength of contraction of diaphragm at the start and after 30 min activity, the percentage of change in strength of muscle contraction & glucose uptake by the diaphragm after 30 min activity and 30 min recovery when compared to the corresponding values of diabetic non-treated group.
Diabetic metformin-treated group revealed statistically significant decrease in fasting serum glucose, glycosylated hemoglobin (HbA1C), HOMA-IR index, serum TNF-α & MDA level; while the total antioxidant capacity, Gast wt/ Tib L ratio, the in vitro strength of contraction of diaphragm at the start and after 30 min activity, the percentage of change in strength of muscle contraction & glucose uptake by the diaphragm after 30 min activity and 30 min recovery were significantly higher when compared to the corresponding values of diabetic non-treated group. However the fasting serum insulin was statistically insignificant.
Upon comparing the results of diabetic metformin-treated group to that of diabetic quercetin-treated group it can be seen that the fasting serum glucose, glycosylated hemoglobin (HbA1C), HOMA-IR index and total antioxidant capacity were significantly lower; while serum TNF-α, MDA level, Gast wt/ Tib L ratio, the in vitro strength of contraction of diaphragm at the start and after 30 min activity & glucose uptake by the -
diaphragm after 30 min activity and 30 min recovery were significantly higher when compared to the corresponding values of diabetic quercetin-treated group. However the fasting serum insulin & the percentage of change in strength of muscle contraction were statistically insignificant.
Diabetic combined quercetin & metformin-treated group showed significant decrease in the fasting serum glucose, glycosylated hemoglobin (HbA1C), HOMA-IR index, serum TNF-α & MDA level & significant increase in the total antioxidant capacity , Gast wt/ Tib L ratio, the in vitro strength of contraction of diaphragm at the start and after 30 min activity, the percentage of change in strength of muscle contraction & glucose uptake by the diaphragm after 30 min activity and 30 min recovery when compared to the corresponding value of diabetic non-treated, diabetic quercetin-treated & diabetic metformin-treated groups. The improvement in all previously investigated parameters can be explained on the basis of combination of hypoglycemic effect of metformin in addition to the hypoglycemic, antioxidant and anti-inflammatory effects of quercetin.
from the previous results it can be concluded that quercetin treatment improved the glycemic state as it decreased fasting serum glucose, glycosylated hemoglobin and decreased insulin resistance in diabetic rats; however the hypoglycemic effect of quercetin is weaker than specific agents as metformin. Combined quercetin treatment with metformin resulted in significant improvement in the glycemic state, insulin resistance and skeletal muscle performance in diabetic rats; this improvement was better than that of using each of them alone. This may indicate that quercetin had a complementary effect to metformin treatment and is a promising adjuvant therapy for type II diabetes mellitus.