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Related Concept Videos

Cells and Secretions of the Pancreas01:16

Cells and Secretions of the Pancreas

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The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
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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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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

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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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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Updated: Jun 2, 2025

Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors
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Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell function.

Livia Lopez-Noriega1, Rebecca Callingham1, Aida Martinez-Sánchez1

  • 1Section of Cell Biology and Functional Genomics, Department of Medicine, Endocrinology and Metabolism, Imperial College London, London, UK.

Iscience
|January 15, 2025
PubMed
Summary
This summary is machine-generated.

A novel long non-coding RNA, Pax6os1/PAX6-AS1, is upregulated in type 2 diabetes and high glucose conditions. Its silencing improves beta cell function, particularly in human cells.

Keywords:
Cell biologyCellular physiologyMolecular biology

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Area of Science:

  • * Molecular Endocrinology
  • * RNA Biology
  • * Diabetes Research

Background:

  • * Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cellular regulation.
  • * Beta cell dysfunction is central to type 2 diabetes pathogenesis.
  • * Understanding novel regulatory mechanisms in beta cells is crucial for therapeutic development.

Purpose of the Study:

  • * To investigate the role of the lncRNA Pax6os1/PAX6-AS1 in beta cell function.
  • * To determine the impact of Pax6os1/PAX6-AS1 expression on beta cell gene regulation and function under metabolic stress.
  • * To explore potential interspecies differences in the function of Pax6os1/PAX6-AS1.

Main Methods:

  • * Analysis of Pax6os1/PAX6-AS1 expression in human and murine beta cell lines and islets under high glucose and high-fat diet conditions.
  • * Gene silencing and overexpression experiments in beta cells.
  • * Assessment of beta cell signature genes, protein translation, and histone modifications.
  • * Phenotypic analysis in Pax6os1 knockout mice and human islets.

Main Results:

  • * Pax6os1/PAX6-AS1 expression is upregulated by high glucose, high-fat diets, and observed in type 2 diabetes.
  • * Silencing Pax6os1/PAX6-AS1 enhances beta cell signature gene expression and improves glucose-stimulated insulin secretion and calcium dynamics in human islets.
  • * Pax6os1/PAX6-AS1 interacts with translation factors (EIF3D) and histones (H3, H4), suggesting roles in translation and epigenetic regulation.
  • * Interspecies differences observed, with a more pronounced effect in human beta cells.

Conclusions:

  • * Pax6os1/PAX6-AS1 is a key regulator of beta cell function, implicated in type 2 diabetes.
  • * Modulation of Pax6os1/PAX6-AS1 offers a potential therapeutic strategy for type 2 diabetes.
  • * The lncRNA exhibits species-specific regulatory roles in beta cells.