Journal
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Volume 13, Issue 5, Pages 1530-+Publisher
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2022.01.008
Keywords
Islets; Insulin; Splice Variants; Gallbladder Development; Differentiation
Categories
Funding
- 2008-2009 British Council (UK-India Educational Research Initiative) exchange program
- National Health and Medical Research Council
- Danish Diabetes Academy visiting professorship
- Australian Research Council
- Juvenile Diabetes Research Foundation (JDRF) Australian Type 1 Diabetes Clinical Research Network (a special initiative of the Australian Research Council) [4-CDA2016-228-MB]
- JDRF USA postdoctoral fellowship (2012-2014)
- advanced post-doctoral fellowship (2015-2018)
- JDRF career transition award (2019-2021)
- University of Sydney
- Australian postgraduate award (University Post-graduate Award or Australian Post-graduate Award)
- JDRF Australia PhD top-up awards
- Council of Scientific and Industrial Research fellowships (Government of India)
- Leona M. and Harry B. Helmsley Charitable Trust [2018PG-T1D009]
- JDRF Australian Type 1 Diabetes Clinical Research Network grant [3-SRA-2019-694-M-B]
- National Health and Medical Research Council Clinical Trials Centre, University of Sydney
Ask authors/readers for more resources
This study reveals the presence of functional insulin-producing cells in the epithelial cells of the gallbladder, both during development and adulthood. Interestingly, these insulin-producing cells in the gallbladder are not targeted by autoimmune cells in a mouse model of type 1 diabetes. These findings highlight the evolutionary and developmental similarities between the gallbladder and the pancreas, and provide potential insights for type 1 diabetes therapy.
BACKGROUND & AIMS: Pancreatic islet beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available