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Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.

ABSTRACT: Background:Osteopontin (Opn) is one of the co-factors involved in cell adhesion and invasion during the implantation process. Several reports have shown Opn expression changes in diabetic condition in several tissues. In addition, an increased incidence of spontaneous abortion is reported in diabetic women. We, therefore, designed a study to evaluate the effects of diabetes on Opn expression at implantation time after treatment with metformin and pioglitazone. Materials and Methods:In this interventional and experimental study, 28 rats were randomly divided into four groups, namely control, diabetic, pioglitazone-treated diabetic rats and metformin-treated diabetic rats. Streptozotocin (STZ) and nicotinamide (NA) were used to induce type 2 diabetes (T2D). During the implantation window, the endometrium was removed and the expression of Opn was analysed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results:Opn expression was significantly higher (30.70 fold-changes) in the diabetic group in comparison with the control group (P=0.04). Furthermore, the expression of Opn was significantly lower in the diabetic group treated with pioglitazone when compared with the diabetic group (P=0.04). Conclusion:According to the high Opn expression and the possibility of increased adhesion of endometrial epithelial cells, the invasion of blastocyst may be affected and thus reduced. As pioglitazone significantly reversed the upregulation of Opn in diabetic rats, it may be considered as a therapeutic compound for treating T2D.

SUBMITTER: Hosseiny ZS

PROVIDER: S-EPMC6186281 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.

Hosseiny Zeinab Sadat ZS Nikpour Parvaneh P Bakhtiary Abas A Mostafavi Fatemah Sadat FS Matinfar Mohammad M Jahani Mehrnaz M Aboutorabi Roshanak R

International journal of fertility & sterility 20181002 4

<h4>Background</h4>Osteopontin (<i>Opn</i>) is one of the co-factors involved in cell adhesion and invasion during the implantation process. Several reports have shown <i>Opn</i> expression changes in diabetic condition in several tissues. In addition, an increased incidence of spontaneous abortion is reported in diabetic women. We, therefore, designed a study to evaluate the effects of diabetes on <i>Opn</i> expression at implantation time after treatment with metformin and pioglitazone.<h4>Mat ...[more]

PMID: 30291688

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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

Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.

Publications

Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.

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