Metformin's Impact on the Microvascular Response to Insulin

Abstract

Metformin improves insulin’s action on whole body glucose metabolism in various insulin-resistant populations. The detailed cellular mechanism(s) for its metabolic actions are multiple and still incompletely understood. Beyond metabolic actions, metformin also impacts microvascular function. However, the effects of metformin on microvascular function and microvascular insulin action specifically are poorly-defined. In this mini-review, we summarize what is currently known about metformin’s beneficial impact on both microvascular function and the microvascular response to insulin while highlighting methodologic issues in the literature that limit straightforward mechanistic understanding of these effects. We examine potential mechanisms for these effects based on pharmacologically-dosed studies and propose that metformin may improve human microvascular insulin resistance by attenuating oxidative stress, inflammation, and endothelial dysfunction. Finally, we explore several important evidence gaps and discuss avenues for future investigation that may clarify whether metformin’s ability to improve microvascular insulin sensitivity is linked to its positive impact on vascular outcomes.

Updated Organic Composition and Potential Therapeutic Properties of Different Varieties of Olive Leaves from Olea europaea

“…Thiazolidinediones (TZDs) enhance insulin sensitivity in skeletal muscle, liver, and adipose tissue and promote fat redistribution from liver and skeletal muscle to adipocytes [ 58 , 59 , 60 ]. Metformin, the most commonly prescribed drug for diabetes, may also increase insulin sensitivity in peripheral tissues during fasting [ 61 , 62 , 63 , 64 , 65 , 66 ]. One of the mechanisms thought to be behind the protective effect of phenolic compounds on the T2DM is that OLE may increase glucagon-like peptide-1 (GLP-1) secretion both in vivo and in vitro [ 67 ].…”

Potential Therapeutic Properties of Olea europaea Leaves from Selected Cultivars Based on Their Mineral and Organic Profiles

“…Among the TPCs found in the OLEs, hydroxytyrosol (HT) is referred to as the chief compound responsible for the biological properties of oleuropein (OLEP), mainly its high antioxidant potential [ 59 ]. HT has also been associated with innumerous favorable properties such as immuno-protective and antimicrobial activity [ 60 , 61 ], and anti-diabetic [ 62 ], anti-arrhythmic and cardioprotective [ 63 ], hypotensive and anti-atherosclerotic [ 64 ], anti-inflammatory [ 65 ], and antioxidant [ 66 , 67 , 68 ] effects. Besides HT, other phenolic compounds have shown to exhibit antibacterial effects against several strains of bacteria responsible for intestinal and respiratory infections in vitro [ 66 , 69 , 70 , 71 ], with promising results for applications as preservatives in food industry [ 23 , 62 , 72 , 73 ], in particular reducing the growth of Helicobacter pylori, which is associated with peptic ulcers and gastric cancer [ 66 ].…”

Clinical Potential of Hydrogen Sulfide in Peripheral Arterial Disease

“…Although solid evidence is still lacking, statins may also provide benefits to endothelial function and against MVD [ 56 , 57 ]. Pre-clinical studies also showed that anti-diabetic therapies, metformin especially, may preserve/restore endothelium function [ 58 , 59 , 60 , 61 ]. Understanding the mechanisms underlying MVD in PAD patients and finding new treatments and therapeutics targeting MVD specifically may help reduce symptoms and improve quality of life.…”