Metformin – mechanisms of action and use for the treatment of type 2 diabetes mellitus
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2011, Vol 65, Issue 0
Abstract
Metformin is widely used for the treatment of type 2 diabetes mellitus. Although this biguanide derivative has been used for more than 50 years, its mechanism of action has not been fully elucidated. In this article we describe the latest achievements concerning the mechanisms of antihyperglycemic action of metformin. They include: decrease of glucose absorption in the small intestine, increase of glucose transport into cells, decrease in the plasma free fatty acid concentrations and inhibition of gluconeogenesis. Activation of AMP-activated protein kinase (AMPK) plays an important role in these processes. The latest discoveries have revealed mechanisms of anti-atherosclerotic, hypotensive and anticancer action of metformin and its impact on vein endothelial function. The pleiotropic actions of metformin include impact on plasma lipid profile, decrease of oxidative stress, and increase in plasma fibrinolytic activity. Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the [i]SLC22A1[/i] gene) and OCT2 (organic cation transporter 2, encoded by the [i]SLC22A2[/i] gene), respectively. However, MATE1 transporter (multidrug and toxin extrusion 1 protein) is encoded by the [i]SLC47A1[/i] gene and facilitates metformin excretion from these cells into bile and urine. Metformin transporter gene polymorphisms may contribute to significant variation in drug response. Further studies of mechanisms of metformin action could contribute to its wider use for the prevention of type 2 diabetes mellitus, cancer, and Alzheimer’s disease, and for the treatment of type 1 diabetes mellitus, and polycystic ovary syndrome (PCOS).
Authors and Affiliations
Marzena Grzybowska, Joanna Bober, Maria Olszewska
Keywords
Related Articles
- EP ID EP66474
- DOI -
- Views 189
- Downloads 0
The biological role of sulfatides
Sulfatides (3-O-sulfogalactosylceramides, sulfated galactocerebrosides, SM4) are esters of sulfuric acid with galactosylceramides. These acidic glycosphingolipids, present at the external leaflet of the plasma membrane,...
Activity of urine arylsulfatase A in brain-dead graft donors is a predictor of early and late graft function
Objective: Human lysosomal arylsulfatase A (ASA) is a member of the sulfatase family. Arylsulfatase A is required to degrade sulfatides. Sulfatides occur in the myelin sheets of the central and peripheral nervous system....
Salivary exoglycosidases in gestational diabetes
Introduction: As exoglycosidases have been described as potential markers of salivary gland pathology, we decided to check the possibility of the use of these enzymes in the detection of salivary gland involvement in ges...
Komórki macierzyste raka płuca – udział w patogenezie i progresji nowotworu
Rak płuca zajmuje pierwsze miejsce wśród przyczyn zgonów na nowotwory złośliwe w Polsce i na świecie. W większości przypadków wysoki stopień zaawansowania choroby w chwili rozpoznania uniemożliwia wdrożenie leczenia przy...
Rola stresu oksydacyjnego w raku pęcherza moczowego
W pracy omówiono wpływ stresu oksydacyjnego i nitracyjnego na szlaki sygnałowe oraz czynniki transkrypcyjne uczestniczące w powstawaniu nowotworów pęcherza. W krajach uprzemysłowionych rak pęcherza moczowego zajmuje czwa...