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Role of pancreatic β-cell death and inflammation in diabetes

机译:胰腺β细胞死亡和炎症在糖尿病中的作用

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Apoptosis of pancreatic β-cells is the final step in the development of type 1 diabetes (T1D), leading to critically diminished β-cell mass and contributing to the onset of hyperglycaemia. The spontaneous apoptosis of pancreatic β-cells during pancreas ontogeny also induces cell death-associated inflammation, stimulates antigen-presenting cells and sensitizes na?ve diabetogenic T cells. The role of pancreatic β-cell death in type 2 diabetes (T2D) is less clear. In the preclinical period of T2D, hyperinsulinaemia and β-cell hyperplasia develop to compensate for insulin resistance, which is clearly seen in animal models of T2D. For the development of overt T2D, relative insulin deficiency is critical in addition to insulin resistance. Insulin deficiency could be due to β-cell dysfunction and/or decreased β-cell mass. Pancreatic β-cell apoptosis due to lipid injury (lipoapoptosis), endoplasmic reticulum (ER) stress or JNK activation could contribute to the decreased β-cell mass in T2D. Activation of inflammasomes by lipid injury, ER stress, human islet amyloid polypeptide, hyperglycaemia or autophagy insufficiency could also lead to β-cell death or dysfunction. Thus, β-cell death and cell death-associated inflammation through innate immune receptors could be important in both T1D and T2D.
机译:胰腺β细胞的凋亡是1型糖尿病(T1D)发展的最后一步,导致β细胞大量减少,并导致高血糖症的发作。胰腺个体发育过程中胰腺β细胞的自发凋亡还诱导与细胞死亡相关的炎症,刺激抗原呈递细胞并使未致糖尿病的T细胞致敏。胰腺β细胞死亡在2型糖尿病(T2D)中的作用尚不清楚。在T2D的临床前期,高胰岛素血症和β细胞增生发展以补偿胰岛素抵抗,这在T2D动物模型中很明显。对于明显的T2D的发展,除了胰岛素抵抗外,相对胰岛素缺乏症也很关键。胰岛素缺乏可能是由于β细胞功能障碍和/或β细胞质量下降所致。脂质损伤(脂质凋亡),内质网(ER)应激或JNK活化引起的胰腺β细胞凋亡可能导致T2D中β细胞质量的降低。脂质损伤,内质网应激,人胰岛淀粉样多肽,高血糖症或自噬功能不足引起的炎性体活化也可能导致β细胞死亡或功能障碍。因此,通过先天免疫受体引起的β细胞死亡和与细胞死亡相关的炎症在T1D和T2D中均可能是重要的。

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