Insulin Resistance as a Therapeutic Target for Improved Endothelial Function:Metformin

Abstract

Endothelial dysfunction is a feature of a variety of clinical states of insulin resistance, and increasingly it is recognized that pre-diabetic states of insulin resistance are associated not only with insulin resistance but with increased cardiovascular risk. The metabolic syndrome which typically accompanies insulin resistance brings aberrations in a number of classical cardiovascular risk factors, but it appears that insulin resistance itself represents an additional, non-classical risk factor. Therefore, the approach to treating the endothelium in patients with the metabolic syndrome might include therapies targeting insulin resistance. In this review, we provide a detailed overview of the current state of knowledge regarding the biguanide metformin and its effects on the endothelium. Its mode of action is reviewed, along with the available data from laboratory and experimental studies related to vascular function in animals and in humans. Metformin has beneficial effects on endothelial function which appear to be mediated through its effects to improve insulin resistance. Therapeutically targeting insulin resistance appears to be a viable route to improving endothelial function in clinical states of insulin resistance.

Pioglitazone Ameliorates Endothelial Dysfunction in Those with Impaired Glucose Regulation among the First-Degree Relatives of Type 2 Diabetes Mellitus Patients

“…Diabetic macroangiopathy is closely related to insulin resistance. Recent studies [ 9 , 10 ] indicate that improvement of insulin resistance is associated with significant improvement of endothelial function. Insulin resistance and endothelial dysfunction are present even in prediabetic subjects.…”

Association between post-ischemic forearm blood flow and blood pressure response to maximal exercise in well trained healthy young men

“…It is well known, in fact, that NO-dependent vasodilatation is altered in subjects with increased peripheral insulin resistance [22], which is related to the fatty body mass [23]. Subjects with higher fat-free body mass, who are expected to have higher peripheral insulin sensitivity [24] may have, therefore, also the most pronounced increase in the NO-dependent flow-mediated vasodilatation.…”

Metformin Attenuated the Autoimmune Disease of the Central Nervous System in Animal Models of Multiple Sclerosis

“…It has anti-inflammatory (14–16) and antioxidant (17–19) properties and the ability to restore endothelial dysfunction (20–22). Metformin mediates its mechanism of action via activation of AMPK.…”