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Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.
Proc. Natl. Acad. Sci. U.S.A. 118:e2107665118 (2021)
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
ISSN (print) / ISBN
0027-8424
e-ISSN
1091-6490
Quellenangaben
Volume: 118,
Issue: 37,
Article Number: e2107665118
Publisher
National Academy of Sciences
Publishing Place
2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Pancreatic Beta Cell Research (IPI)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Diabetes and Regeneration Research (IDR)
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
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