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Kemter, E.* ; Müller, A.* ; Neukam, M. ; Ivanova, A. ; Klymiuk, N.* ; Renner, S.* ; Yang, K. ; Broichhagen, J.* ; Kurome, M.* ; Zakhartchenko, V.* ; Kessler, B.* ; Knoch, K.P.* ; Bickle, M.* ; Ludwig, B.* ; Johnsson, K.* ; Lickert, H. ; Kurth, T.* ; Wolf, E.* ; Solimena, M.

Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.

Proc. Natl. Acad. Sci. U.S.A. 118:e2107665118 (2021)
Postprint DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo-labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Diabetes Mellitus ; Insulin Turnover ; Pig Model ; β Cell; Endocrine Pancreas; 1st-phase; Dynamics; Release; Islets
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 118, Issue: 37, Pages: , Article Number: e2107665118 Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
Institute of Diabetes and Regeneration Research (IDR)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-001
G-501900-231
G-502300-001
Grants European Fund for Regional Development
Core Facility of the CMCB Technology Platform at TU Dresden
German Federal Ministry of Education and Research (BMBF)
German Research Council
DZD by the BMBF
German Research Foundation (DFG)
Agence Nationale de la Recherche
Innovative Medicines Initiative 2 Joint Undertak-ing
European Union's Framework Program Horizon 2020
European Federation of Pharmacological Industries and Associations (EFPIA)
Swiss State Secretariat for Education, Research, and Innovation
Juvenile Diabetes Research Foundation (JDRF) International
Leona M. and Harry B. Helmsley Charitable Trust
Carl Gustav Carus Faculty of Medicine at TU Dresden
Dresden International Graduate School for Biomedicine and Bioengineering
DFG
Light Microscopy Facility
DOI 10.1073/pnas.2107665118
WOS ID WOS:000705153400007
Scopus ID 85114719778
PubMed ID 34508004
Erfassungsdatum 2021-10-14
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