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 150
- Downloads 0
Kannabinoidy a hemostaza
Elementy układu endokannabinoidowego (receptory kannabinoidowe CB1, CB2, CBED i CBPT, endokannabinoidy oraz układy enzymatyczne biorące udział w ich syntezie i metabolizmie) znajdują się w strukturach zaangażowanych w pr...
Rola limfocytów Th17 w patogenezie raka jelita grubego
Szacuje się, że rak jelita grubego (RJG) zajmuje pierwsze miejsce wśród przyczyn zgonów na nowotwory złośliwe u mężczyzn i kobiet w UE. Każdego roku w Polsce odnotowuje się 15 254 nowych przypadków RJG oraz 10 501 przypa...
Different mortality predictor pattern in hemodialysis and peritoneal dialysis diabetic patients in 4-year prospective observation
Introduction: The aim was to identify factors carrying an ominous prognosis in a cohort of diabetic patients (pts) on a hemodialysis (HD) and peritoneal dialysis (PD) program.Materials and methods: We analyzed survival r...
Przydatność oznaczania stężenia prokalcytoniny w porównaniu ze stężeniem białka C-reaktywnego oraz ilością białych krwinek we krwi noworodków w monitorowaniu leczenia uogólnionych zakażeń szpitalnych
Amphibian skin secretions as a new source of antibiotics and biologically active substances
So far, the main sources of biologically active substances used in medicine have been plants, molds, and propolis. The obtained compounds have either therapeutic features or require additional modification. They are some...