Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.
Curr Opin Immunol. 2018 Jun;52:1-7. doi: 10.1016/j.coi.2018.02.002. Epub 2018 Mar 6.
Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines. In human adipocytes, the P2X7 receptor promotes the release of inflammatory cytokines, at least in part via inflammasome activation, likely contributing to systemic insulin resistance. This receptor-inflammasome system is also strongly activated in macrophages infiltrating both pancreas and adipose tissue, mediating a deleterious cross-talk that perpetuates the damage.
2 型糖尿病在全球的发病率正呈惊人之势。其复杂的发病机制肯定包括低度炎症的关键作用，而低度炎症可能是由嘌呤能信号的过度激活引发的。在这种复杂的情况下，细胞外 ATP 会损害两个关键角色的功能：β细胞和脂肪组织。在前者中，P2Y 受体和可能的一些 P2X 受体-离子通道调节胰岛素分泌，但仍存在争议的是，过量的 ATP 是否可以通过 P2X 受体直接损害β细胞功能，或者细胞损伤是否是由于细胞因子的过度系统性释放所致。在人类脂肪细胞中，P2X7 受体促进炎症细胞因子的释放，至少部分是通过炎性小体的激活，可能导致全身胰岛素抵抗。这种受体-炎性小体系统在浸润胰腺和脂肪组织的巨噬细胞中也被强烈激活，介导了一种有害的串扰，从而使损伤持续存在。
