Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Diabetes Research Center, Qatar Biomedical Research Institute, Doha, Qatar.
J Cell Physiol. 2019 Aug;234(8):12551-12561. doi: 10.1002/jcp.28123. Epub 2019 Jan 7.
Statins, with their lipid-lowering properties, are a first-line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new-onset diabetes (NOD). The molecular mechanisms of statin-induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.
他汀类药物具有降低血脂的特性，是预防心血管疾病的一线治疗药物。然而，最近的证据表明，他汀类药物可能会增加新发糖尿病（NOD）的风险。他汀类药物引起的 NOD 的分子机制尚不清楚，尽管已经提出了一些病理生理机制。具体到β细胞，这些机制包括胰岛素分泌的改变、离子通道的变化、信号通路的调节以及炎症/氧化应激。在β细胞之外，其他被认为的机制还包括脂肪细胞，包括脂肪细胞分化的改变以及瘦素和脂联素的调节，以及遗传和表观遗传机制，包括 microRNA 的改变。将讨论支持这些和其他机制的证据。更深入地了解将糖尿病发作与他汀类药物治疗联系起来的潜在机制至关重要，并且具有临床相关性，因为它可能使新的预防或治疗方法得以实施，并指导缺乏这种副作用的新一代他汀类药物的生产。
