Pleiotropic benefits of metformin: macrophage targeting its anti-inflammatory mechanisms.

Abstract

Metformin is a biguanide family member used in the treatment of type 2 diabetes and one of the most widely prescribed antidiabetes drugs. This drug increases the peripheral uptake of glucose, decreases hepatic glucose production, and reduces insulin resistance in liver and skeletal muscle. The exact molecular mechanisms responsible for its effect on glucose homeostasis are still not completely understood but may include the triggering of the AMPK pathway (1), although it has been indicated that the acute inhibitory effects of high doses of metformin on hepatic gluconeogenesis are independent of AMPK activation (2). Interestingly, experimental and clinical studies have shed new light on an array of potential benefits of metformin, not only in the treatment of diabetes. Notably, accumulating evidence suggests that the cardiovascular protective role of metformin is largely beyond its hypoglycemic action and is ascribed to pleiotropic effects (3–5). Previous studies have described the anti-inflammatory effects of metformin on different types of cells, including human vascular endothelial cells and smooth muscle cells (6,7). Recent reports have also demonstrated that metformin can attenuate lipopolysaccharide (LPS)-induced or oxidized LDL–induced proinflammatory responses in monocytes and macrophages (8,9). Although the crucial mechanisms underlying the anti-inflammatory effects of metformin remain to be fully elucidated, the current concept of atherosclerosis as an inflammatory disorder may imply that such anti-inflammatory properties could contribute, at least in part, to the anti-atherosclerotic …