Cellular and molecular mechanisms of metformin: an overview
| Autor: | Benoit Viollet, Fabrizio Andreelli, Jocelyne Leclerc, Marc Foretz, Bruno Guigas, Nieves Sanz Garcia |
|---|---|
| Přispěvatelé: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Cell Biology, Leiden University Medical Center (LUMC), Service de diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Société Francophone du Diabète (SFD), Agence Nationale de la Recherche [grant number 2010 BLAN 1123], European Commission integrated project [grant number LSHMCT- 2004-005272/exgenesis], European Project: 28783,EXGENESIS, Universiteit Leiden-Universiteit Leiden, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Viollet, Benoit, Health benefits of exercise: identification of genes and signalling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome - EXGENESIS - 28783 - OLD |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
endocrine system diseases
Type 2 diabetes Pharmacology 0302 clinical medicine Neoplasms mitochondrion Diabetic Nephropathies [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 0303 health sciences Biguanide Fatty liver MESH: cancer General Medicine [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Polycystic ovary MESH: cardiovascular system 3. Good health Metformin Gestational diabetes Mitochondrial respiratory chain 030220 oncology & carcinogenesis Female medicine.drug Polycystic Ovary Syndrome MESH: metabolism medicine.medical_specialty medicine.drug_class Biology Article 03 medical and health sciences Internal medicine Circadian Clocks AMP-activated protein kinase (AMPK) medicine Animals Humans Hypoglycemic Agents cancer 030304 developmental biology MESH: Type 2 diabetes MESH: AMPK AMPK nutritional and metabolic diseases MESH: mitochondrion medicine.disease Endocrinology cardiovascular system MESH: metformin metformin metabolism |
| Zdroj: | Clinical Science Clinical Science, Portland Press, 2012, 122 (6), pp.253-70. ⟨10.1042/CS20110386⟩ Clinical Science, 2012, 122 (6), pp.253-70. ⟨10.1042/CS20110386⟩ CLINICAL SCIENCE, 122(5-6), 253-270 |
| ISSN: | 0143-5221 1470-8736 |
| DOI: | 10.1042/CS20110386⟩ |
| Popis: | 8 pages; International audience; Considerable efforts have been made since the 1950s to better understand the cellular and molecular mechanisms of action of metformin, a potent antihyperglycaemic agent now recommended as the first-line oral therapy for T2D (Type 2 diabetes). The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. In addition, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, providing a generally accepted mechanism for the action of metformin on hepatic gluconeogenesis. The demonstration that respiratory chain complex I, but not AMPK, is the primary target of metformin was recently strengthened by showing that the metabolic effect of the drug is preserved in liver-specific AMPK-deficient mice. Beyond its effect on glucose metabolism, metformin has been reported to restore ovarian function in PCOS (polycystic ovary syndrome), reduce fatty liver, and to lower microvascular and macrovascular complications associated with T2D. Its use has also recently been suggested as an adjuvant treatment for cancer or gestational diabetes and for the prevention in pre-diabetic populations. These emerging new therapeutic areas for metformin will be reviewed together with recent findings from pharmacogenetic studies linking genetic variations to drug response, a promising new step towards personalized medicine in the treatment of T2D. |
| Databáze: | OpenAIRE |
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