Metformin also induces a profound shift in the faecal microbial community profile in diabetic mice, and this may contribute to its mode of action possibly through an effect on glucagon-like peptide-1 secretion.In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake (by inducing the phosphorylation of GLUT4 enhancer factor), decreases insulin-induced suppression of fatty acid oxidation, and decreases the absorption of glucose from the gastrointestinal tract. Increased peripheral use of glucose may be due to improved insulin binding to insulin receptors. The increase in insulin binding after metformin treatment has also been demonstrated in patients with diabetes mellitus type 2.AMPK probably also plays a role in increased peripheral insulin sensitivity, as metformin administration increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. Some metabolic actions of metformin do appear to occur by AMPK-independent mechanisms. Metformin has indirect antiandrogenic effects in women with insulin resistance, such as those with PCOS, due to its beneficial effects on insulin sensitivity. It may reduce testosterone levels in such women by as much as 50%. A Cochrane review, though, found that metformin was only slightly effective for decreasing androgen levels in women with PCOS.Metformin also has significant effects on the gut microbiome, such as its effect on increasing agmatine production by gut bacteria, but the relative importance of this mechanism compared to other mechanisms is uncertain. Pharmacokinetics
Metformin has an oral bioavailability of 50–60% under fasting conditions, and is absorbed slowly.
This allows the complex surgery to proceed in a still environment.Due to the physiological stress associated with open-heart surgery, elderly and very sick patients may be subject to increased risk, and may not be candidates for this type of surgery. As a consequence, there are attempts to identify means of correcting MR on a beating heart. The Alfieri technique for instance, has been replicated using a percutaneous catheter technique, which installs a "MitraClip" device to hold the middle of the mitral valve closed.Indications for surgery for chronic MR include signs of left ventricular dysfunction with ejection fraction less than 60%, severe pulmonary hypertension with pulmonary artery systolic pressure greater than 50 mmHg at rest or 60 mmHg during activity, and new-onset atrial fibrillation. Epidemiology
Significant mitral valve regurgitation has a prevalence of approximately 2% of the population, affecting males and females equally. It is one of the two most common valvular heart diseases in the elderly, and the commonest type of valvular heart disease in low and middle income countries.In a study of 595 male elite football players aged 18–38 and 47 sedentary non-athletes, mitral regurgitation was found in 20% football players and 15% in control group. Football players with mitral regurgitation were found to have larger mitral annulus diameter compared to athletes without regurgitation, and left atrium diameter was larger in athletes with MR.

See also
Tricuspid regurgitation
Aortic regurgitation
Pulmonary insufficiency

References


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