A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary
Background & Aims: Pancreatic islet β-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-produ...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X2200008X |
| _version_ | 1818050819392536576 |
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| author | Mugdha V. Joglekar Subhshri Sahu Wilson K.M. Wong Sarang N. Satoor Charlotte X. Dong Ryan J. Farr Michael D. Williams Prapti Pandya Gaurang Jhala Sundy N.Y. Yang Yi Vee Chew Nicola Hetherington Dhan Thiruchevlam Sasikala Mitnala Guduru V. Rao Duvvuru Nageshwar Reddy Thomas Loudovaris Wayne J. Hawthorne Andrew G. Elefanty Vinay M. Joglekar Edouard G. Stanley David Martin Helen E. Thomas David Tosh Louise T. Dalgaard Anandwardhan A. Hardikar |
| author_facet | Mugdha V. Joglekar Subhshri Sahu Wilson K.M. Wong Sarang N. Satoor Charlotte X. Dong Ryan J. Farr Michael D. Williams Prapti Pandya Gaurang Jhala Sundy N.Y. Yang Yi Vee Chew Nicola Hetherington Dhan Thiruchevlam Sasikala Mitnala Guduru V. Rao Duvvuru Nageshwar Reddy Thomas Loudovaris Wayne J. Hawthorne Andrew G. Elefanty Vinay M. Joglekar Edouard G. Stanley David Martin Helen E. Thomas David Tosh Louise T. Dalgaard Anandwardhan A. Hardikar |
| author_sort | Mugdha V. Joglekar |
| collection | DOAJ |
| description | Background & Aims: Pancreatic islet β-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-producing cells. Methods: We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assays, RNA sequencing, real-time polymerase chain reaction, chromatin immunoprecipitation, and functional studies. Results: We show that the epithelial lining of developing, as well as adult, mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucose in vitro and in situ. Notably, in a non-obese diabetic (NOD) mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Interestingly, in human gallbladders, insulin splice variants are absent, although insulin splice forms are observed in human islets. Conclusions: In summary, our biochemical, transcriptomic, and functional data in mouse and human gallbladder epithelial cells collectively show the evolutionary and developmental similarities between gallbladder and the pancreas that allow gallbladder epithelial cells to continue insulin production in adult life. Understanding the mechanisms regulating insulin transcription and translation in gallbladder epithelial cells would help guide future studies in type 1 diabetes therapy. |
| first_indexed | 2024-12-10T10:59:32Z |
| format | Article |
| id | doaj.art-3d728a223a8941f1b6deb7467c5a4e8a |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-10T10:59:32Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-3d728a223a8941f1b6deb7467c5a4e8a2022-12-22T01:51:44ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2022-01-0113515301553.e4A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummaryMugdha V. Joglekar0Subhshri Sahu1Wilson K.M. Wong2Sarang N. Satoor3Charlotte X. Dong4Ryan J. Farr5Michael D. Williams6Prapti Pandya7Gaurang Jhala8Sundy N.Y. Yang9Yi Vee Chew10Nicola Hetherington11Dhan Thiruchevlam12Sasikala Mitnala13Guduru V. Rao14Duvvuru Nageshwar Reddy15Thomas Loudovaris16Wayne J. Hawthorne17Andrew G. Elefanty18Vinay M. Joglekar19Edouard G. Stanley20David Martin21Helen E. Thomas22David Tosh23Louise T. Dalgaard24Anandwardhan A. Hardikar25Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaImmunology and Diabetes Group, St. Vincent’s Institute for Medical Research, Victoria, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaThe Westmead Institute for Medical Research, Westmead Millenium Institute, University of Sydney, Westmead, New South Wales, AustraliaDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, AustraliaDepartment of Gastroenterology, St. Vincent’s Hospital, Melbourne, Victoria, AustraliaSurgical Gastroenterology Research, Asian Institute of Gastroenterology, Hyderabad, IndiaSurgical Gastroenterology Research, Asian Institute of Gastroenterology, Hyderabad, IndiaSurgical Gastroenterology Research, Asian Institute of Gastroenterology, Hyderabad, IndiaImmunology and Diabetes Group, St. Vincent’s Institute for Medical Research, Victoria, AustraliaThe Westmead Institute for Medical Research, Westmead Millenium Institute, University of Sydney, Westmead, New South Wales, AustraliaMurdoch Childrens Research Institute, Parkville, Victoria, AustraliaShree Seva Medical Foundation, Shirwal, IndiaMurdoch Childrens Research Institute, Parkville, Victoria, AustraliaUpper Gastrointestinal Surgery, Strathfield Hospital, Strathfield, New South Wales, AustraliaImmunology and Diabetes Group, St. Vincent’s Institute for Medical Research, Victoria, AustraliaDepartment of Biology and Biochemistry, University of Bath, Bath, United KingdomSection of Eukaryotic Cell Biology, Department of Science and Environment, Roskilde University, Roskilde, DenmarkDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia; Correspondence Address correspondence to: Anandwardhan A. Hardikar, PhD, Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, 30.2.27 Goldsmith and David Pilgrim Avenue, Campbelltown, New South Wales 2560, Australia. fax: (61) 2 4620 3891.Background & Aims: Pancreatic islet β-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-producing cells. Methods: We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assays, RNA sequencing, real-time polymerase chain reaction, chromatin immunoprecipitation, and functional studies. Results: We show that the epithelial lining of developing, as well as adult, mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucose in vitro and in situ. Notably, in a non-obese diabetic (NOD) mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Interestingly, in human gallbladders, insulin splice variants are absent, although insulin splice forms are observed in human islets. Conclusions: In summary, our biochemical, transcriptomic, and functional data in mouse and human gallbladder epithelial cells collectively show the evolutionary and developmental similarities between gallbladder and the pancreas that allow gallbladder epithelial cells to continue insulin production in adult life. Understanding the mechanisms regulating insulin transcription and translation in gallbladder epithelial cells would help guide future studies in type 1 diabetes therapy.http://www.sciencedirect.com/science/article/pii/S2352345X2200008XIsletsInsulinSplice VariantsGallbladder DevelopmentDifferentiation |
| spellingShingle | Mugdha V. Joglekar Subhshri Sahu Wilson K.M. Wong Sarang N. Satoor Charlotte X. Dong Ryan J. Farr Michael D. Williams Prapti Pandya Gaurang Jhala Sundy N.Y. Yang Yi Vee Chew Nicola Hetherington Dhan Thiruchevlam Sasikala Mitnala Guduru V. Rao Duvvuru Nageshwar Reddy Thomas Loudovaris Wayne J. Hawthorne Andrew G. Elefanty Vinay M. Joglekar Edouard G. Stanley David Martin Helen E. Thomas David Tosh Louise T. Dalgaard Anandwardhan A. Hardikar A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary Cellular and Molecular Gastroenterology and Hepatology Islets Insulin Splice Variants Gallbladder Development Differentiation |
| title | A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary |
| title_full | A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary |
| title_fullStr | A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary |
| title_full_unstemmed | A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary |
| title_short | A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsSummary |
| title_sort | pro endocrine pancreatic islet transcriptional program established during development is retained in human gallbladder epithelial cellssummary |
| topic | Islets Insulin Splice Variants Gallbladder Development Differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X2200008X |
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