Role of lipotoxicity in vascular and β-cell damage in type 2 diabetes
Abstract
Background. Diabetes is a complex disease which currently affects 425 million people worldwide and type 2 diabetes (T2D) accounts for 80-90% of all cases. Development and progression of T2D is caused by insulin resistance (IR) and pancreatic β-cell failure, the latter due to dysfunction or destruction of β-cells. Nevertheless, the most prevalent cause of mortality in T2D patients is represented by cardiovascular (CV) disease which occurs with two-three times higher rate in these subjects than in adults without diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) – in particular empagliflozin, dapagliflozin and canagliflozin – belong to a recently introduced class of anti-diabetic drugs capable to improve both hyperglycemia and CV risk. The mechanisms underlying SGLT2-I-mediated CV protection are still unclear but, among other hypotheses, it has been proposed the inhibition of the sodium/H+ exchanger (NHE) as putative non-canonical mediator of SGLT2-I-mediated effects. A key phenomenon in the pathogenesis of both IR, β-cell dysfunction and CV risk, is represented by lipotoxicity, which consists in the deleterious effects caused by elevated free fatty acid (FFA) levels. The present study focuses on the possible effects of lipotoxicity on two cell types directly involved in (1) vascular complication, with specific focus on impaired reparatory mechanisms, and (2) progression of β-cell dysfunction. As a cell population with a pivotal role in endothelial repair,…
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