Research Unit, Hospital Universitario de Canarias, 38320 La Laguna, Santa Cruz de Tenerife, Spain.
Fundación General de la Universidad, Universidad de La Laguna, 38204 La Laguna, Santa Cruz de Tenerife, Spain.
Int J Mol Sci. 2021 Sep 24;22(19):10311. doi: 10.3390/ijms221910311.
The combination of insulin resistance and β-cells dysfunction leads to the onset of type-2 diabetes mellitus (T2DM). This process can last for decades, as β-cells are able to compensate the demand for insulin and maintain normoglycemia. Understanding the adaptive capacity of β-cells during this process and the causes of its failure is essential to the limit onset of diabetes. Post-transplant diabetes mellitus (PTDM) is a common and serious disease that affects 30% of renal transplant recipients. With the exception of immunosuppressive therapy, the risk factors for T2D are the same as for PTDM: obesity, dyslipidaemia, insulin resistance and metabolic syndrome. Tacrolimus (TAC) is the immunosuppressant of choice after renal transplantation but it has the highest rates of PTDM. Our group has shown that insulin resistance and glucolipotoxicity, without favouring the appearance of apoptosis, modify key nuclear factors for the maintenance of identity and functionality of β-cells. In this context, TAC accelerates or enhances these changes. Our hypothesis is that the pathways that are affected in the progression from pre-diabetes to diabetes in the general population are the same pathways that are affected by TAC. So, TAC can be considered a tool to study the pathogenesis of T2DM. Here, we review the common pathways of β-cells dysfunction on T2DM and TAC-induced diabetes.
胰岛素抵抗和β细胞功能障碍的结合导致 2 型糖尿病（T2DM）的发生。这个过程可以持续几十年，因为β细胞能够补偿胰岛素的需求并维持正常血糖水平。了解β细胞在此过程中的适应能力及其衰竭的原因对于限制糖尿病的发生至关重要。移植后糖尿病（PTDM）是一种常见且严重的疾病，影响 30%的肾移植受者。除免疫抑制治疗外，T2D 的危险因素与 PTDM 相同：肥胖、血脂异常、胰岛素抵抗和代谢综合征。他克莫司（TAC）是肾移植后的首选免疫抑制剂，但它导致 PTDM 的发生率最高。我们的研究小组已经表明，胰岛素抵抗和糖脂毒性不会促进细胞凋亡，但会改变β细胞维持其特性和功能的关键核因子。在这种情况下，TAC 会加速或增强这些变化。我们的假设是，在一般人群中从糖尿病前期进展到糖尿病的过程中受影响的途径与 TAC 受影响的途径相同。因此，TAC 可以被视为研究 T2DM 发病机制的工具。在这里，我们回顾了 T2DM 和 TAC 诱导的糖尿病中β细胞功能障碍的常见途径。
