Dataset Information

Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.

ABSTRACT:

Background

Polycystic ovary syndrome (PCO) is recognized as the most common endocrinopathy in female. Chemerin is a novel adipocytokine that is expressed in ovary and upregulated in adipose tissue of obese, PCO patients. To date there is no report about the regulation of ovarian chemerin gene expression after PCO induction and treatment by insulin sensitizing drugs including pioglitazone and metformin. Thirty female rats were divided into six experimental groups with five rats in each group including control group, PCO group (i.m injection of 4 mg estradiol benzoate for 40 days), metformin treated (200 mg/kg/day for 21 days), pioglitazone treated (20 mg/kg/day, for 21 days), PCO?+?metformin and PCO?+?pioglitazone. PCO was detected by microscopic observation of vaginal smear and treatment by metformin and pioglitazone was initiated one week after that. Ovarian chemerin expression was analyzed by real time PCR and western blotting.

Results

Our results demonstrated that PCO induction resulted in elevation of chemerin mRNA and protein levels in ovary in concomitant with incidence of insulin resistance and increasing androgen and progesterone production. We observed that metformin and pioglitazone attenuated ovarian chemerin expression and improved insulin resistance and abnormal steroid production in PCO rats.

Conclusion

Based on data presented here we concluded that alteration of ovarian chemerin expression may has important role in PCO development and manipulation of chemerin expression or signaling by pioglitazone or metformin can be a novel therapeutic mechanism in the treatment of PCO patients by these drugs.

SUBMITTER: Kabiri N

PROVIDER: S-EPMC4008382 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Publications

Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.

Kabiri Nahid N Tabandeh Mohammad Reza MR Tabatabaie Seyed Reza Fatemi SR

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20140424

<h4>Background</h4>Polycystic ovary syndrome (PCO) is recognized as the most common endocrinopathy in female. Chemerin is a novel adipocytokine that is expressed in ovary and upregulated in adipose tissue of obese, PCO patients. To date there is no report about the regulation of ovarian chemerin gene expression after PCO induction and treatment by insulin sensitizing drugs including pioglitazone and metformin. Thirty female rats were divided into six experimental groups with five rats in each gr ...[more]

PMID: 24762064

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Project description:BACKGROUND:The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA?+?DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin. METHODS:In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA?+?DHA concentrate (5 g/day, containing ~2.8 g EPA?+?DHA; Omega-3), or (iv) pioglitazone and EPA?+?DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA?+?DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers. RESULTS:Omega-3 and Pio& Omega-3 increased EPA?+?DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3. CONCLUSION:Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA?+?DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy. TRIAL REGISTRATION:EudraCT number 2009-011106-42.

Dataset Information

Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.

Background

Results

Conclusion

Publications

Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.

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