الفهرس 
AIntroduction And Aim OF The workOnly 14 pages are availabe for public view
 |  | from | 268 |  |  |
| | | from | 268 | | |
Abstract
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
The aim of this study is to evaluate dapagliflozin efficacy as a new anti-diabetic drug and test its effects on body weight, blood lipid profile, liver functions, kidney functions and oxidative stress in comparison with standard anti-diabetic drugs like glimepiride and pioglitazone. Also, evaluation of potential benefits from combination of dapagliflozin with resveratrol in treatment of type 2 diabetes induced in rats.
In the current study we evaluated the effect of oral daily treatment with dapagliflozin orally in a dose of 1 mg/kg/day for 8 weeks, glimepiride orally in a dose of 0.1 mg/kg daily for 8 weeks, resveratrol orally in a dose of 20 mg/kg daily for 8 weeks, pioglitazone orally in a dose of 10 mg/kg for 8 weeks and combinations from the previous drugs orally at the same doses and duration, in type 2 DM experimentally induced in rats by high fat diet and 2 low doses of streptozotocin.
Rats in the diabetic control group (group 2) (in whom type 2 DM is induced by high fat diet for 4 weeks followed by 2 low doses of streptozotocin. Then received 1 ml of distilled water orally together with the high fat diet for 8 weeks ,without any treatment), these showed the highest mean blood glucose (405.6 ± 34.42), the lowest mean insulin level (5.52 ± 0.49) and the highest mean insulin resistance (5.53 ± 0.47).
In the above mentioned doses:
1-Rats received dapagliflozin (group 3) showed significantly lower mean blood glucose (275.1 ± 25.92), higher mean insulin level (5.95 ± 0.55) and lower mean insulin resistance (4.04 ± 0.32). Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
2-Rats received glimepiride (group 4) showed significantly lower mean blood glucose (264.5 ± 24.68), higher mean insulin level (6.51 ± 0.61) and lower mean insulin resistance (4.25 ± 0.35). Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function and pancreatic beta cell function.
3-Rats received resveratrol (group 5) showed significantly lower mean blood glucose (280.6 ± 26.84), higher mean insulin level (6.32 ± 0.57) and lower mean insulin resistance (4.38 ± 0.37). Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, liver function, antioxidants and pancreatic beta cell function.
4-Rats received pioglitazone (group 6) showed significantly lower mean blood glucose (257.6 ± 23.52), higher mean insulin level (6.02 ± 0.58) and lower mean insulin resistance (3.83 ± 0.31). Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
5-Rats received combination of dapagliflozin and resveratrol (group 7) showed significantly lower mean blood glucose (230.7 ± 21.27), higher mean insulin level (6.46 ± 0.6) and lower mean insulin resistance (3.68 ± 0.29) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
6- Rats received combination of glimepiride and pioglitazone (group 8) showed significantly lower mean blood glucose (221.5 ± 21.32), higher mean insulin level (6.63 ± 0.62) and lower mean insulin resistance (3.63 ± 0.27) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
7- Rats received combination of dapagliflozin and glimepiride (group 9) showed significantly lower mean blood glucose (225.2 ± 20.77), higher mean insulin level (6.68 ± 0.59) and lower mean insulin resistance (3.71 ± 0.31) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
8- Rats received combination of dapagliflozin and pioglitazone (group 10) showed significantly lower mean blood glucose (227.1 ± 21.36), higher mean insulin level (6.49 ± 0.55) and lower mean insulin resistance (3.64 ± 0.22) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
9- Rats received combination of dapagliflozin, pioglitazone and glimepiride (group 11) showed significantly lower mean blood glucose (217.4 ± 18.25), higher mean insulin level (6.71 ± 0.63) and lower mean insulin resistance (3.59 ± 0.28) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
10- Rats received combination of dapagliflozin, pioglitazone, resveratrol and glimepiride (group 12) showed significantly lower mean blood glucose (212.6 ± 18.56), higher mean insulin level (6.75 ± 0.64) and lower mean insulin resistance (3.54 ± 0.25) with significant increase in efficacy compared to effect achieved by each drug given alone. Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, liver functions, antioxidants and pancreatic beta cell function.
The results of our study indicated the following:
1- Oral administration of dapagliflozin in a dose of 10 mg/kg/day For 8 weeks significantly decreased blood glucose and improved insulin resistance in comparison to the diabetic control group. Its antidiabetic effect is nearly similar to standard antidiabetic medications like glimepiride and pioglitazone. Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
2- Oral administration of resveratrol in a dose of 20 mg/kg/day For 8 weeks significantly decreased blood glucose and improved insulin resistance in comparison to the diabetic control group. Its antidiabetic effect is close to standard antidiabetic medications like glimepiride and pioglitazone. Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, liver function, antioxidants and pancreatic beta cell function.
3- Oral administration of resveratrol in a dose of 20 mg/kg/day in combination with dapagliflozin in a dose of 10 mg/kg/day for 8 weeks showed significantly more antidiabetic effect than that of resveratrol or dapagliflozin alone in comparison to the diabetic control group and their antidiabetic effect in combination is close to the antidiabetic effect of combination of standard antidiabetic medications like glimepiride and pioglitazone. Treatment caused significant reduction of body weight, blood lipids, oxidative stress and significant improvement of kidney function, antioxidants and pancreatic beta cell function.
In Conclusion, Dapagliflozin and resveratrol have a good antidiabetic effect against high fat diet plus low dose streptozotocin-induced type 2 diabetes in male albino rats. This antidiabetic effect increases with combination of both and becomes close to the antidiabetic effect of standard antidiabetic drugs like glimepiride and pioglitazone with an advantage of resveratrol being natural and more safe. Also, combination of dapagliflozin and resveratrol has other advantage beyond antidiabetic effect including lowering of blood lipids, renoprotective effect and hepatoprotective effect.