For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
26
views
473
references
 Top references
cited by
14
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      235
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function in women with polycystic ovary syndrome (PCOS) and improves fetal development, pregnancy outcomes and offspring health in gestational diabetes mellitus (GDM) and T2DM. MF treatment is demonstrated to improve the efficiency of in vitro fertilization and is considered a supplementary drug in assisted reproductive technologies. MF administration shows positive effect on steroidogenesis and spermatogenesis in men with metabolic disorders, thus MF treatment indicates prospective use for improvement of male reproductive functions and fertility. MF lacks teratogenic effects and has positive health effect in newborns. The review is focused on use of MF therapy for restoration of female and male reproductive functions and improvement of pregnancy outcomes in metabolic and endocrine disorders. The mechanisms of MF action are discussed, including normalization of metabolic and hormonal status in PCOS, GDM, T2DM and metabolic syndrome and restoration of functional activity and hormonal regulation of the gonadal axis.

          Related collections

          Most cited references473

          • Record: found
          • Abstract: found
          • Article: not found

          AMPK: a nutrient and energy sensor that maintains energy homeostasis.

          D Hardie, Fiona Ross, Simon A. Hawley (2012)
          AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.
          Article 0 comments Cited 727 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Role of AMP-activated protein kinase in mechanism of metformin action.

            J Ventre, G. Zhou, R. Myers … (2001)
            Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.
            Article 0 comments Cited 545 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The mechanisms of action of metformin

              Graham Rena, D Hardie, Ewan Pearson (2017)
              Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes. Electronic supplementary material The online version of this article (doi:10.1007/s00125-017-4342-z) contains a slideset of the figures for download, which is available to authorised users.
              Article 0 comments Cited 532 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceuticals (Basel)
                Journal ID (iso-abbrev): Pharmaceuticals (Basel)
                Journal ID (publisher-id): pharmaceuticals
                Title: Pharmaceuticals
                Publisher: MDPI
                ISSN (Electronic): 1424-8247
                Publication date (Electronic): 08 January 2021
                Publication date Collection: January 2021
                Volume: 14
                Issue: 1
                Electronic Location Identifier: 42
                Affiliations
                I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia; alex_shpakov@ 123456list.ru ; Tel.: +7-812-5523117
                Article
                Publisher ID: pharmaceuticals-14-00042
                DOI: 10.3390/ph14010042
                PMC ID: 7826885
                PubMed ID: 33429918
                SO-VID: b8b2d06e-de1d-4ee4-87b4-c1de7d2fe717
                Copyright © © 2021 by the author.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 11 November 2020
                Date accepted : 06 January 2021
                Categories
                Subject: Review

                Keywords: metformin,diabetes mellitus,gestational diabetes mellitus,polycystic ovary syndrome,in vitro fertilization,ovary,testes,insulin,gonadotropin,folliculogenesis,steroidogenesis
                Data availability:
                Keywords: metformin, diabetes mellitus, gestational diabetes mellitus, polycystic ovary syndrome, in vitro fertilization, ovary, testes, insulin, gonadotropin, folliculogenesis, steroidogenesis

                Comments

                Comment on this article

                scite_

                Similar content235

                See all similar

                Cited by13

                See all cited by

                Most referenced authors5,469

                See all reference authors