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Schubert, U. ; Lehmann, S. ; Schmid, J. ; Morawietz, H.* ; Bornstein, S.R. ; Ludwig, B.

The adrenal gland and pancreatic islets - a beneficial endocrine alliance.

Horm. Metab. Res. 56, 286-293 (2024)
DOI PMC
Intraportal islet transplantation in patients with type 1 diabetes enables restoration of glucose-regulated insulin secretion. However, several factors hamper a widespread application and long-term success: chronic hypoxia, an inappropriate microenvironment and suppression of regenerative and proliferative potential by high local levels of immunosuppressive agents. Therefore, the identification of alternative and superior transplant sites is of major scientific and clinical interest. Here, we aim to evaluate the adrenal as an alternative transplantation site. The adrenal features a particular microenvironment with extensive vascularization, anti-apoptotic and pro-proliferative, anti-inflammatory and immunosuppressive effects. To validate this novel transplantation site, an in vitro co-culture system of adrenal cells and pancreatic islets was established and viability, islet survival, functional potency and antioxidative defense capacity were evaluated. For in vivo validation, an immune-deficient diabetic mouse model for intra-adrenal islet transplantation was applied. The functional capacity of intra-adrenally grafted islets to reverse diabetes was compared to a standard islet transplant model and measures of engraftment such as vascular integration were evaluated. The presence of adrenal cells positively impacted on cell metabolism and oxidative stress. Following transplantation, we could demonstrate enhanced islet function in comparison to standard models with improved engraftment and superior re-vascularization. This experimental approach allows for novel insights into the interaction of endocrine systems and may open up novel strategies for islet transplantation augmented through the bystander effect of other endocrine cells or the active factors secreted by adrenal cells modulating the microenvironment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diabetes ; Diabetes ; Microenvironment ; Site ; Transplantation; Cell-death; Adrenomedullin; Hormone; Stress
ISSN (print) / ISBN 0018-5043
e-ISSN 1439-4286
Zeitschrift Hormone and Metabolic Research
Quellenangaben Band: 56, Heft: 4, Seiten: 286-293 Artikelnummer: , Supplement: ,
Verlag Thieme
Verlagsort Rudigerstr 14, D-70469 Stuttgart, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)
Förderungen Deutsche Forschungsgemeinschaft
Centre for Regenerative Therapies Dresden
Paul Langerhans Institute Dresden
German Center for Diabetes Research (DZD)