RESUMEN
Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.
Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/patología , Células Secretoras de Insulina/virología , Receptores de Coronavirus/metabolismo , SARS-CoV-2/aislamiento & purificación , Serina Endopeptidasas/metabolismo , Adulto , Anciano , Autopsia , Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/virología , Diabetes Mellitus/patología , Dipeptidil Peptidasa 4/metabolismo , Femenino , Proteínas HMGN/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Persona de Mediana Edad , Neuropilina-1/metabolismo , Especificidad de Órganos/fisiologíaRESUMEN
The mammalian adrenal gland is composed of two distinct tissue types in a bidirectional connection, the catecholamine-producing medulla derived from the neural crest and the mesoderm-derived cortex producing steroids. The medulla mainly consists of chromaffin cells derived from multipotent nerve-associated descendants of Schwann cell precursors. Already during adrenal organogenesis, close interactions between cortex and medulla are necessary for proper differentiation and morphogenesis of the gland. Moreover, communication between the cortex and the medulla ensures a regular function of the adult adrenal. In tumor development, interfaces between the two parts are also common. Here, we summarize the development of the mammalian adrenal medulla and the current understanding of the cortical-medullary interactions under development and in health and disease.