Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life

Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state of cellular transdifferentiation, enabling an increase in beta-cell mass in response to severe metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated th...

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Main Authors: Jiwon Hahm, Dawn Kumar, Juan Andres Fernandez Andrade, Edith Arany, David J. Hill
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/1/34
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author Jiwon Hahm
Dawn Kumar
Juan Andres Fernandez Andrade
Edith Arany
David J. Hill
author_facet Jiwon Hahm
Dawn Kumar
Juan Andres Fernandez Andrade
Edith Arany
David J. Hill
author_sort Jiwon Hahm
collection DOAJ
description Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state of cellular transdifferentiation, enabling an increase in beta-cell mass in response to severe metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated the ontogeny of bi-hormonal islet endocrine cell populations throughout the human lifespan. Immunofluorescence microscopy was performed for insulin, glucagon, and somatostatin presence on paraffin-embedded sections of pancreata from 20 donors without diabetes aged between 11 days and 79 years of age. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunoreactive cells within islets was 27.5%, 62.1%, and 12.1%, respectively. There was no change in the relative presence of alpha- or beta-cells with advancing age, but delta-cell presence showed a decline with age (R<sup>2</sup> = 0.59, <i>p</i> < 0.001). The most abundant bi-hormonal cell phenotype observed co-stained for glucagon and insulin, representing 3.1 ± 0.3% of all islet cells. Glucagon/somatostatin and insulin/somatostatin bi-hormonal cells were also observed representing 2–3% abundance relative to islet cell number. Glucagon/insulin bi-hormonal cells increased with age (R<sup>2</sup> = 0.30, <i>p</i> < 0.05) whilst insulin/somatostatin (R<sup>2</sup> = 0.50, <i>p</i> < 0.01) and glucagon/somatostatin (R<sup>2</sup> = 0.35, <i>p</i> < 0.05) cells decreased with age of donor. Findings show that bi-hormonal cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity.
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spelling doaj-art-da00cbffd6b54555a5c19661d1d2c90c2025-01-10T13:16:19ZengMDPI AGCells2073-44092025-01-011413410.3390/cells14010034Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout LifeJiwon Hahm0Dawn Kumar1Juan Andres Fernandez Andrade2Edith Arany3David J. Hill4Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, CanadaLawson Health Research Institute, St. Joseph’s Health Care, London, ON N6A 4V2, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, CanadaLawson Health Research Institute, St. Joseph’s Health Care, London, ON N6A 4V2, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, CanadaBi-hormonal islet endocrine cells have been proposed to represent an intermediate state of cellular transdifferentiation, enabling an increase in beta-cell mass in response to severe metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated the ontogeny of bi-hormonal islet endocrine cell populations throughout the human lifespan. Immunofluorescence microscopy was performed for insulin, glucagon, and somatostatin presence on paraffin-embedded sections of pancreata from 20 donors without diabetes aged between 11 days and 79 years of age. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunoreactive cells within islets was 27.5%, 62.1%, and 12.1%, respectively. There was no change in the relative presence of alpha- or beta-cells with advancing age, but delta-cell presence showed a decline with age (R<sup>2</sup> = 0.59, <i>p</i> < 0.001). The most abundant bi-hormonal cell phenotype observed co-stained for glucagon and insulin, representing 3.1 ± 0.3% of all islet cells. Glucagon/somatostatin and insulin/somatostatin bi-hormonal cells were also observed representing 2–3% abundance relative to islet cell number. Glucagon/insulin bi-hormonal cells increased with age (R<sup>2</sup> = 0.30, <i>p</i> < 0.05) whilst insulin/somatostatin (R<sup>2</sup> = 0.50, <i>p</i> < 0.01) and glucagon/somatostatin (R<sup>2</sup> = 0.35, <i>p</i> < 0.05) cells decreased with age of donor. Findings show that bi-hormonal cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity.https://www.mdpi.com/2073-4409/14/1/34humanpancreasislets of Langerhansbi-hormonal cellsinsulinlifespan
spellingShingle Jiwon Hahm
Dawn Kumar
Juan Andres Fernandez Andrade
Edith Arany
David J. Hill
Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
Cells
human
pancreas
islets of Langerhans
bi-hormonal cells
insulin
lifespan
title Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
title_full Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
title_fullStr Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
title_full_unstemmed Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
title_short Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life
title_sort bi hormonal endocrine cell presence within the islets of langerhans of the human pancreas throughout life
topic human
pancreas
islets of Langerhans
bi-hormonal cells
insulin
lifespan
url https://www.mdpi.com/2073-4409/14/1/34
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AT juanandresfernandezandrade bihormonalendocrinecellpresencewithintheisletsoflangerhansofthehumanpancreasthroughoutlife
AT editharany bihormonalendocrinecellpresencewithintheisletsoflangerhansofthehumanpancreasthroughoutlife
AT davidjhill bihormonalendocrinecellpresencewithintheisletsoflangerhansofthehumanpancreasthroughoutlife