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      Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

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          Abstract

          Background

          Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM.

          Methods

          Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, ELISA was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight.

          Results

          Oleuropein attenuated the elevated body weight of GDM mice and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment.

          Conclusions

          Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.

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          Most cited references34

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          Metabolism of inflammation limited by AMPK and pseudo-starvation.

          Metabolic changes in cells that participate in inflammation, such as activated macrophages and T-helper 17 cells, include a shift towards enhanced glucose uptake, glycolysis and increased activity of the pentose phosphate pathway. Opposing roles in these changes for hypoxia-inducible factor 1α and AMP-activated protein kinase have been proposed. By contrast, anti-inflammatory cells, such as M2 macrophages, regulatory T cells and quiescent memory T cells, have lower glycolytic rates and higher levels of oxidative metabolism. Some anti-inflammatory agents might act by inducing, through activation of AMP-activated protein kinase, a state akin to pseudo-starvation. Altered metabolism may thus participate in the signal-directed programs that promote or inhibit inflammation.
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            Adherence to Mediterranean Diet and Risk of Cancer: An Updated Systematic Review and Meta-Analysis

            The aim of the present systematic review and meta-analysis was to gain further insight into the effects of adherence to Mediterranean Diet (MedD) on risk of overall cancer mortality, risk of different types of cancer, and cancer mortality and recurrence risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and Scopus until 25 August 2017. We included randomized trials (RCTs), cohort (for specific tumors only incidence cases were used) studies, and case-control studies. Study-specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effects model. Observational studies (cohort and case-control studies), and intervention trials were meta-analyzed separately. The updated review process showed 27 studies that were not included in the previous meta-analysis (total number of studies evaluated: 83 studies). An overall population of 2,130,753 subjects was included in the present update. The highest adherence score to a MedD was inversely associated with a lower risk of cancer mortality (RRcohort: 0.86, 95% CI 0.81 to 0.91, I 2 = 82%; n = 14 studies), colorectal cancer (RRobservational: 0.82, 95% CI 0.75 to 0.88, I 2 = 73%; n = 11 studies), breast cancer (RRRCT: 0.43, 95% CI 0.21 to 0.88, n = 1 study) (RRobservational: 0.92, 95% CI 0.87 to 0.96, I 2 = 22%, n = 16 studies), gastric cancer (RRobservational: 0.72, 95% CI 0.60 to 0.86, I 2 = 55%; n = 4 studies), liver cancer (RRobservational: 0.58, 95% CI 0.46 to 0.73, I 2 = 0%; n = 2 studies), head and neck cancer (RRobservational: 0.49, 95% CI 0.37 to 0.66, I 2 = 87%; n = 7 studies), and prostate cancer (RRobservational: 0.96, 95% CI 0.92 to 1.00, I 2 = 0%; n = 6 studies). Among cancer survivors, the association between the adherence to the highest MedD category and risk of cancer mortality, and cancer recurrence was not statistically significant. Pooled analyses of individual components of the MedD revealed that the protective effects appear to be most attributable to fruits, vegetables, and whole grains. The updated meta-analysis confirms an important inverse association between adherence to a MedD and cancer mortality and risk of several cancer types, especially colorectal cancer. These observed beneficial effects are mainly driven by higher intakes of fruits, vegetables, and whole grains. Moreover, we were able to report for the first time a small decrease in breast cancer risk (6%) by pooling seven cohort studies.
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              Gestational diabetes mellitus.

              (2004)
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                January 2021
                30 November 2020
                : 10
                : 1
                : 45-53
                Affiliations
                [1 ]Department of Obstetrics and Gynecology , Liaocheng People’s Hospital, Liaocheng, Shandong, China
                Author notes
                Correspondence should be addressed to A Wang: wangaixia12@ 123456163.com

                *(Z Zhang and H Zhao contributed equally to this work)

                Article
                EC-20-0466
                10.1530/EC-20-0466
                7923051
                33289688
                b4ee5970-70ad-4f4d-81b0-7bf126472c71
                © 2021 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 13 October 2020
                : 30 November 2020
                Categories
                Research

                oleuropein,gestational diabetes mellitus,oxidative stress,inflammation,ampk signaling

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