PDF(Pubmed)
Abstract：
Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (β) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor β. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.
摘要：
有证据表明，COVID-19患者或疫苗与糖代谢功能障碍之间存在关联，糖尿病发生的风险更高。在这里，我们回顾性分析了2020年至2023年的67例SARS-CoV-2感染的非人灵长类动物(NHP)模型和121例接种和感染的NHP以及COVID-19患者的尸检组织中的胰腺病变.多标记免疫荧光显示病毒在NHP和人类中直接感染外分泌和内分泌胰腺细胞。在成人模型中观察到轻微和有限的表型和组织病理学变化。系统蛋白质组学和代谢组学结果表明代谢紊乱，主要富含胰岛素抵抗途径，在受感染的成人NHP中，同时空腹C肽和C肽/葡萄糖比率水平升高。此外，在老年COVID-19NHP中，SARS-CoV-2感染导致β（β）细胞丢失和原位胰岛素表达降低，其特征是胰岛淀粉样变性和坏死。α-SMA的激活和加重的纤维化，包括血清中的低胶原，胰腺炎症和应激标志物的增加，ICAM-1和G3BP1，以及更严重的糖代谢功能障碍。相比之下,疫苗接种通过激活胰岛素受体α和胰岛素受体β维持葡萄糖稳态。总的来说,COVID-19后糖尿病的累积风险与年龄密切相关，提示应重视老年COVID-19患者的血糖管理。
