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Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Efficient Generation of Pancreas/Duodenum Homeobox Protein 1+ Posterior Foregut/Pancreatic Progenitors from hPSCs in Adhesion Cultures
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A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human

Mugdha V Joglekar1, Subhshri Sahu1, Wilson K M Wong1

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Summary

Gallbladder epithelial cells in mice and humans can produce and release insulin, functioning similarly to pancreatic cells. These gallbladder insulin-producing cells are not attacked in type 1 diabetes models, offering potential therapeutic insights.

Keywords:
DifferentiationGallbladder DevelopmentInsulinIsletsSplice Variants

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Area of Science:

  • Endocrinology
  • Developmental Biology
  • Cell Biology

Background:

  • Pancreatic beta-cells are primary insulin producers, but ectopic insulin expression occurs elsewhere.
  • The gallbladder's proximity to the developing pancreas suggests a potential functional link.

Purpose of the Study:

  • To investigate the presence and function of insulin-producing cells within the gallbladder epithelium.
  • To compare gallbladder and pancreatic insulin production mechanisms.

Main Methods:

  • Immunohistochemistry, flow cytometry, ELISA, RNA sequencing, qPCR, ChIP, and functional assays were employed.
  • Developing and adult mouse and human gallbladder and islet cells were analyzed.

Main Results:

  • Gallbladder epithelial cells in both developing and adult mice and humans contain insulin-producing cells capable of transcription, translation, packaging, and release.
  • Human gallbladder cells demonstrated glucose-responsive insulin secretion in vitro and in situ.
  • In a non-obese diabetic mouse model, gallbladder insulin-producing cells were not subject to autoimmune attack.
  • Human gallbladders lack insulin splice variants, unlike human islets.

Conclusions:

  • Biochemical, transcriptomic, and functional data reveal evolutionary and developmental similarities between the gallbladder and pancreas, enabling gallbladder insulin production in adults.
  • Understanding gallbladder insulin regulation mechanisms could inform future type 1 diabetes therapies.