A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics
Abstract Physiological changes during pregnancy support foetal growth, including adaptations in pancreatic islets to maintain glucose homeostasis. We investigate these adaptations using rare, high-quality pancreatic tissue from pregnant human donors and matched controls. We profile islets from pregn...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61852-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332418709815296 |
|---|---|
| author | Faheem Seedat Katie Holden Simon Davis Roman Fischer James Bancroft Edward Drydale Neva Kandzija John A. Todd Manu Vatish M. Irina Stefana |
| author_facet | Faheem Seedat Katie Holden Simon Davis Roman Fischer James Bancroft Edward Drydale Neva Kandzija John A. Todd Manu Vatish M. Irina Stefana |
| author_sort | Faheem Seedat |
| collection | DOAJ |
| description | Abstract Physiological changes during pregnancy support foetal growth, including adaptations in pancreatic islets to maintain glucose homeostasis. We investigate these adaptations using rare, high-quality pancreatic tissue from pregnant human donors and matched controls. We profile islets from pregnant donors using proteomics and assess α- and β-cell characteristics, as well as prolactin receptor and serotonin 2B receptor expression. Proteomic profiling of microdissected human islets identifies 7546 proteins but shows minimal differences in protein expression. In pregnancy, we show that islet area increases 1.9-fold, α- and β-cell areas increase 4.3- and 1.9-fold, driven by an increase in cell number rather than hypertrophy. Prolactin receptor expression is higher in α but not β cells, and serotonin 2B receptor is undetectable in β cells. Glucagon-like peptide-1 abundance increases 2.9-fold in α cells. These findings indicate that the molecular mechanisms driving pregnancy-induced islet adaptations in humans differ from those in mice, highlighting the need for human-based studies. |
| format | Article |
| id | doaj-art-d819dd250cd44351a5fe87192ae2c67c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d819dd250cd44351a5fe87192ae2c67c2025-08-20T03:46:12ZengNature PortfolioNature Communications2041-17232025-07-0116112310.1038/s41467-025-61852-5A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomicsFaheem Seedat0Katie Holden1Simon Davis2Roman Fischer3James Bancroft4Edward Drydale5Neva Kandzija6John A. Todd7Manu Vatish8M. Irina Stefana9Centre for Human Genetics, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of OxfordTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordNuffield Department of Women’s and Reproductive Health, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordAbstract Physiological changes during pregnancy support foetal growth, including adaptations in pancreatic islets to maintain glucose homeostasis. We investigate these adaptations using rare, high-quality pancreatic tissue from pregnant human donors and matched controls. We profile islets from pregnant donors using proteomics and assess α- and β-cell characteristics, as well as prolactin receptor and serotonin 2B receptor expression. Proteomic profiling of microdissected human islets identifies 7546 proteins but shows minimal differences in protein expression. In pregnancy, we show that islet area increases 1.9-fold, α- and β-cell areas increase 4.3- and 1.9-fold, driven by an increase in cell number rather than hypertrophy. Prolactin receptor expression is higher in α but not β cells, and serotonin 2B receptor is undetectable in β cells. Glucagon-like peptide-1 abundance increases 2.9-fold in α cells. These findings indicate that the molecular mechanisms driving pregnancy-induced islet adaptations in humans differ from those in mice, highlighting the need for human-based studies.https://doi.org/10.1038/s41467-025-61852-5 |
| spellingShingle | Faheem Seedat Katie Holden Simon Davis Roman Fischer James Bancroft Edward Drydale Neva Kandzija John A. Todd Manu Vatish M. Irina Stefana A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics Nature Communications |
| title | A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics |
| title_full | A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics |
| title_fullStr | A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics |
| title_full_unstemmed | A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics |
| title_short | A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics |
| title_sort | new paradigm of islet adaptations in human pregnancy insights from immunohistochemistry and proteomics |
| url | https://doi.org/10.1038/s41467-025-61852-5 |
| work_keys_str_mv | AT faheemseedat anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT katieholden anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT simondavis anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT romanfischer anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT jamesbancroft anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT edwarddrydale anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT nevakandzija anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT johnatodd anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT manuvatish anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT mirinastefana anewparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT faheemseedat newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT katieholden newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT simondavis newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT romanfischer newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT jamesbancroft newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT edwarddrydale newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT nevakandzija newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT johnatodd newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT manuvatish newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics AT mirinastefana newparadigmofisletadaptationsinhumanpregnancyinsightsfromimmunohistochemistryandproteomics |