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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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Related Experiment Video

Updated: Jul 11, 2025

A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination
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Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.

Emily K Sims1, Abhishek Kulkarni2, Audrey Hull3

  • 1Division of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Cell Reports. Medicine
|November 2, 2023
PubMed
Summary

Alpha-difluoromethylornithine (DFMO) shows promise in delaying type 1 diabetes (T1D) by protecting beta cells. This study confirms its safety and suggests DFMO may preserve beta cell function in T1D patients.

Keywords:
disease modificationisletornithine decarboxylasepolyaminespreventiontrialtype 1 diabetesα-difluoromethylornithineβ cellβ cell stress

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Area of Science:

  • Endocrinology
  • Immunology
  • Metabolic Diseases

Background:

  • Alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, has shown potential in preclinical models to delay type 1 diabetes (T1D) onset.
  • The precise mechanism of DFMO's action and its tolerability in humans have remained unclear.

Purpose of the Study:

  • To investigate the cell-autonomous role of ODC in beta cell stress.
  • To evaluate the safety and efficacy of DFMO in preserving beta cell function in recent-onset T1D patients.

Main Methods:

  • Mice with beta cell-specific ODC deletion were assessed for protection against toxin-induced diabetes.
  • A randomized controlled trial (NCT02384889) evaluated DFMO safety and tolerability in 41 recent-onset T1D subjects over 3 months.
  • Urinary putrescine levels, C-peptide levels, and islet cell gene/protein expression were analyzed.

Main Results:

  • Beta cell ODC deletion protected mice from toxin-induced diabetes, indicating a cell-autonomous role.
  • DFMO was found to be safe and well-tolerated in T1D patients, meeting the primary outcome.
  • DFMO dose-dependently reduced urinary putrescine and preserved C-peptide levels at higher doses, without significant immunomodulation.
  • Transcriptomic and proteomic analyses of DFMO-treated human islets revealed modulation of mRNA translation, protein transport, and secretion pathways.

Conclusions:

  • DFMO demonstrates safety and tolerability in recent-onset T1D patients.
  • The findings suggest DFMO may preserve beta cell function in T1D through cell-autonomous mechanisms involving protein synthesis and secretion pathways.