Lipotoxicity versus adipotoxicity—The deleterious effects of adipose tissue on beta cells in the pathogenesis of type 2 diabetes

Type 2 diabetes (T2D) is thought to be a culmination of two seemingly distinct processes, insulin resistance and beta cell failure, both of which have been closely linked to obesity. Here, we focus on the various deleterious effects of obesity on the beta cell. Obesity can affect beta cells directly through the influence of elevated levels of free fatty acids (FFA), or remotely through the newly termed group of cytokines that are secreted by adipose tissue-adipokines. The direct effect of free fatty acids, termed lipotoxicity, is thought to be the result of activation of multiple intracellular signals in the beta cell, eventually leading to apoptosis and reduced insulin secretion. The remote effect of obesity is thought to be mediated by adipokines such as TNF-alpha, IL-6, leptin, omentin, visfatin, adipsin, resistin, apelin and retinol binding protein (rbp4). The currently known effects of these adipokines on beta cell function and survival are reviewed here.