Post 9wtGTDsZVDcu4U0w76 by Jopo89@mas.to
 (DIR) More posts by Jopo89@mas.to
 (DIR) Post #9wtFxMd1RCg5wKY8B6 by Jopo89@mas.to
       2020-07-08T22:42:15Z
       
       0 likes, 1 repeats
       
       Lactic Acidosis & Metformin. Metformin is a diabetic drug used to reduce liver gluconeogenesis via hepatic AMPK enzymes. However it has a direct effect on mitochondria. Although the exact mechanism is not clearly known (and transport inside the mitochondria double matrix varies according to carrier protein and time of day) clinically relevant doses of metformin WILL affect Complex I of the ETC. The key thing about this complex is electrons can pass forward as well backwards through it
       
 (DIR) Post #9wtGEYh7pTMIHkfSZU by Jopo89@mas.to
       2020-07-08T22:45:21Z
       
       0 likes, 1 repeats
       
       This is reverse electron transfer and it blasts free radicals everywhere. Metformin inhibits this complex and can reduce reverse electron transfer however in absence of  forward flow also through the ETC no ATP is generated from aerobic respiration and TCA Substrates accumulate. Only lactate based metabolism is then possible. So metformin can cause profound lactic acidosis. Curiously it does however protect in chronic inflammation and confers survival benefit secondary to ROS inhibition
       
 (DIR) Post #9wtGTDsZVDcu4U0w76 by Jopo89@mas.to
       2020-07-08T22:48:00Z
       
       0 likes, 1 repeats
       
       In addition to glucose effects. Don’t  if been used in sepsis? Metformin toxicity is under diagnosed and should be considered in AKI/renal accumulation in an odd lactate situation. It is reversible and improves with filtration. It has potential to give a false impression of illness severity if not addressed. Mitochondrial inhibition was originally part of reason not ideal post MI for a few days. #medicine #FOAMed #science