Unidad de Investigación Biomédica, Delegación Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, México.
Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autonóma de San Luis Potosí, San Luis Potosí, México.
Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1092-1100. doi: 10.1111/1440-1681.13147. Epub 2019 Aug 20.
The pathogenesis of type 2 diabetes (T2D) is associated with a progressive loss of pancreatic β-cell mass. It is known that miR-146a, miR-34a, and miR-375 are involved in β-cell functionality. In this work, we evaluated the levels of these miRNAs in normal-glycaemic individuals, pre-diabetic, and T2D patients in relation to β-cell functionality, insulin resistance, and metabolic parameters. The relative expression of the miRNAs was evaluated in serum samples by real-time polymerase chain reaction. In a principal component analysis, we observed that T2D patients and pre-diabetic individuals were not associated with β-cell functionality. However, in a correlation matrix analysis, we detected that miR-34a was related to miR-146a and insulin resistance. The relative expression of miR-375 was correlated with cholesterol and low-density lipoprotein levels. A decrease of β-cell function in pre-diabetic individuals and T2D patients was observed. The insulin resistance was higher in pre-diabetic individuals and T2D patients. The relative expression of miR-146a in pre-diabetic individuals, T2D patients with insulin treatment, and T2D patients with nephropathy and diabetic foot was decreased. In addition, miR-34a was increased in T2D patients who were overweight and obese. The relative expression of miR-375 was increased in T2D patients with poor glycaemic control, while a decrease was seen in T2D patients with nephropathy and diabetic foot. Circulating miR-375, miR-34a, and miR-146a were not associated with β-cell functionality, but their expression was differentially affected by glycaemia, obesity, insulin treatment, and the presence of nephropathy and diabetic foot.
2 型糖尿病（T2D）的发病机制与胰腺β细胞数量的进行性丧失有关。已知 miR-146a、miR-34a 和 miR-375 参与β细胞功能。在这项工作中，我们评估了这些 miRNA 在正常血糖个体、糖尿病前期和 T2D 患者中的水平与β细胞功能、胰岛素抵抗和代谢参数的关系。通过实时聚合酶链反应评估了 miRNA 在血清样本中的相对表达。在主成分分析中，我们观察到 T2D 患者和糖尿病前期患者与β细胞功能无关。然而，在相关矩阵分析中，我们发现 miR-34a 与 miR-146a 和胰岛素抵抗相关。miR-375 的相对表达与胆固醇和低密度脂蛋白水平相关。在糖尿病前期和 T2D 患者中观察到β细胞功能下降。糖尿病前期和 T2D 患者的胰岛素抵抗更高。糖尿病前期个体、接受胰岛素治疗的 T2D 患者和患有肾病和糖尿病足的 T2D 患者的 miR-146a 相对表达降低。此外，超重和肥胖的 T2D 患者中 miR-34a 增加。血糖控制不佳的 T2D 患者中 miR-375 的相对表达增加，而患有肾病和糖尿病足的 T2D 患者中 miR-375 的相对表达降低。循环 miR-375、miR-34a 和 miR-146a 与β细胞功能无关，但它们的表达受血糖、肥胖、胰岛素治疗以及肾病和糖尿病足的存在的差异影响。
