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Related Concept Videos

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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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Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
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Related Experiment Video

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Single-cell RNA Sequencing and Analysis of Human Pancreatic Islets
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Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study.

Ahmed M Abdellatif1,2,3, Heather Jensen Smith4,5, Robert Z Harms1,2

  • 1Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, United States.

Frontiers in Immunology
|November 30, 2019
PubMed
Summary

Gut bacteria like Bacteroides dorei and Ruminococcus gnavus may trigger inflammation in pancreatic islets, potentially contributing to type 1 diabetes (T1D) development. This study reveals how these bacteria impact islet gene expression and immune responses.

Keywords:
Bacteroides doreiRuminococcus gnavusautoimmunitydysbiosistype 1 diabetesβ-cell

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Area of Science:

  • Immunology
  • Microbiology
  • Endocrinology

Background:

  • Type 1 diabetes (T1D) involves autoimmune destruction of pancreatic beta cells.
  • Distinct intestinal microbiome profiles are observed in T1D subjects.
  • The link between gut microbial homeostasis and T1D pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the hypothesis that gut bacteria constituents can induce inflammation and metabolic abnormalities in human islets.
  • To explore the impact of specific gut bacteria, Bacteroides dorei (BD) and Ruminococcus gnavus (RG), on human islet gene expression.

Main Methods:

  • Human islets were exposed to BD and RG in vitro.
  • RNA-sequencing (RNA-Seq) was performed to analyze gene expression changes.
  • Ingenuity pathway analysis (IPA) was used to identify affected biological pathways.
  • Immunoblotting and ELISA confirmed the expression of selected factors.

Main Results:

  • Exposure to BD and RG significantly altered human islet gene expression.
  • Commonly upregulated genes included cytokines, chemokines, and enzymes, indicating effects on antimicrobial and biosynthetic pathways.
  • IPA revealed activation of TREM1 signaling and inflammatory response pathways.
  • Each bacterium induced a unique set of differentially expressed genes (DEGs).
  • Increased levels of specific factors were validated experimentally.

Conclusions:

  • Human islets mount a complex antibacterial response to gut bacteria.
  • This response involves both symbiotic and pathogenic aspects, with prominent oxidative damage and leukocyte recruitment factors.
  • Bacterial-induced islet inflammation and potential beta cell damage may contribute to T1D autoimmunity.