Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome

Udesen, Pernille Bækgaard; Glintborg, Dorte; Sørensen, Anja Elaine; Svendsen, Rikke Pilsgaard; Nielsen, Nanna Louise Skov; Wissing, Marie Louise Muff; Andersen, Marianne; Englund, Anne Lis Mikkelsen; Dalgaard, Louise Torp

doi:10.1530/ec-20-0195

Cited by 23 publications

(17 citation statements)

References 47 publications

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“…This result is in line with the study by Gillet et al which showed that pregnancies affected by GDM were associated with elevated serum exosomal miR-122 early in gestation (6-15 weeks of gestation) [28]. Several studies have shown that increased miR-122 is associated with obesity, insulin resistance, metabolic syndrome [80][81][82], while metformin treatment [66] and weight loss [83] results in a reduction of miR-122-5p. We demonstrate in our study that insulin sensitivity, measured through OGIS, and HDL cholesterol were negatively correlated with miR-122-5p, while offspring birthweight was positively correlated with miR-122-5p, thus further strengthening the role of miR-122 as a marker of impaired metabolic health.…”

Section: Discussionsupporting

confidence: 90%

“…Liver [62], skeletal muscle [63], beta cell [64] and adipose tissue [65] miR-29a levels are increased in states of insulin resistance and hyperglycemia. Accordingly, circulating miR-29a decreases upon metformin treatment [66]. Therefore, it is conceivable that the increased early pregnancy miR-29a levels, as well as the other differentially expressed miRNAs in women who later develop GDM, could be an indicator of a general impaired metabolic state.…”

Section: Discussionmentioning

confidence: 99%

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The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Sørensen

Poppel

Desoyé

et al. 2021

Cells

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Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter ‘Vitamin D and lifestyle intervention for GDM prevention (DALI)’ trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Sørensen

Poppel

Desoyé

et al. 2021

Cells

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“…However, at present, there is little evidence that these circulating miRNAs are involved in GLUT4 expression or IR [135]. In a study in PCOS patients, 12-month metformin treatment reduced serum levels of miR-122, miR-223, and miR-29a, all of which have previously been reported to influence glucose metabolism [136].…”

Section: Epigenetic Modificationsmentioning

confidence: 97%

Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport

Herman

Kravos

Jensterle

et al. 2022

IJMS

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Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity. There is a well-documented correlation between glucose transporter 4 (GLUT4) expression and the level of IR. Therefore, the observed increase in peripheral glucose utilization after metformin treatment most likely comes from the induction of GLUT4 expression and its increased translocation to the plasma membrane. However, the mechanisms behind this effect and the critical metformin targets are still largely undefined. The present review explores the evidence for the crucial role of changes in the expression and activation of insulin signaling pathway mediators, AMPK, several GLUT4 translocation mediators, and the effect of posttranscriptional modifications based on previously published preclinical and clinical models of metformin’s mode of action in animal and human studies. Our aim is to provide a comprehensive review of the studies in this field in order to shed some light on the complex interactions between metformin action, GLUT4 expression, GLUT4 translocation, and the observed increase in peripheral insulin sensitivity.

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“…A research found that the overexpression of miR-122 in the serum of patients with PCOS with impaired glucose tolerance was significantly associated with those without impaired glucose tolerance, and it is closely related to the regulation of insulin signaling pathway (48). Udesen and colleagues found that miR-122 was significantly reduced in the serum of women with PCOS after metformin treatment, and this report also suggests that miR-122 regulation may be related to insulin sensitivity (49). These all suggest that the regulation of miR-122 is crucial for the diagnosis and treatment of PCOS with insulin resistance, but the specific mechanism remains confused.…”

Section: Discussionmentioning

confidence: 90%

Differential expression of microRNA in the serum of patients with polycystic ovary syndrome with insulin resistance

Huang¹,

Ji²,

Ye³

et al. 2022

Ann Transl Med

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Background: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease in women of childbearing age, and insulin resistance is an important etiological mechanism in PCOS. This study revealed the microRNA (miRNA) expression profile of PCOS with insulin resistance and explored the potential biological functions of differentially expressed miRNA.Methods: A total of 76 patients with PCOS and 30 normal healthy women were recruited in the gynecological clinic of the Second Hospital of Tianjin Medical University. We divided the patients with PCOS into a group with insulin resistance (n=46) and a group without insulin resistance (n=30). Peripheral venous serum samples from each group were used for deep sequencing to identify differentially expressed miRNAs. Hierarchical clustering heat maps were used to show differences in miRNA expression. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and target gene network databases were used to explore the potential target genes of differentially expressed miRNAs and to analyze their specific biological functions.Results: A case-control analysis found that the levels of body mass index (BMI), prolactin (PRL), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (INS) in patients with PCOS were higher than those in healthy controls. High BMI, high blood sugar, and hyperinsulinemia were more significant in the PCOS with insulin resistance group than without insulin resistance group. Among the patients with PCOS, miR-122-5p was found to have more significant differences in the PCOS with insulin resistance group. GO and KEGG pathway analysis showed that the identified miRNAs were involved in the regulation of different biological processes, such as signal transduction, negative regulation of GTPase activity, chloride channel complex. The predicted target genes were related to the citrate cycle (TCA cycle) and the biosynthesis of mucin-type O-glycans.Conclusions: Our research demonstrated the use of miRNAs as new biomarkers for the diagnosis, treatment and presented a new strategy to lessen the symptoms of PCOS with insulin resistance.

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Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome

Cited by 23 publications

References 47 publications

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport

Differential expression of microRNA in the serum of patients with polycystic ovary syndrome with insulin resistance

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