Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models
Mohamed Saleh, … , Krishna Prasadan, George K. Gittes
Mohamed Saleh, … , Krishna Prasadan, George K. Gittes
Published December 22, 2020
Citation Information: J Clin Invest. 2021;131(3):e143301. https://doi.org/10.1172/JCI143301.
View: Text | PDF
Research Article Endocrinology Gastroenterology

Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models

  • Text
  • PDF
Abstract

Chronic pancreatitis affects over 250,000 people in the US and millions worldwide. It is associated with chronic debilitating pain, pancreatic exocrine failure, and high risk of pancreatic cancer and usually progresses to diabetes. Treatment options are limited and ineffective. We developed a new potential therapy, wherein a pancreatic ductal infusion of 1%–2% acetic acid in mice and nonhuman primates resulted in a nonregenerative, near-complete ablation of the exocrine pancreas, with complete preservation of the islets. Pancreatic ductal infusion of acetic acid in a mouse model of chronic pancreatitis led to resolution of chronic inflammation and pancreatitis-associated pain. Furthermore, acetic acid–treated animals showed improved glucose tolerance and insulin secretion. The loss of exocrine tissue in this procedure would not typically require further management in patients with chronic pancreatitis because they usually have pancreatic exocrine failure requiring dietary enzyme supplements. Thus, this procedure, which should be readily translatable to humans through an endoscopic retrograde cholangiopancreatography (ERCP), may offer a potential innovative nonsurgical therapy for chronic pancreatitis that relieves pain and prevents the progression of pancreatic diabetes.

Authors

Mohamed Saleh, Kartikeya Sharma, Ranjeet Kalsi, Joseph Fusco, Anuradha Sehrawat, Jami L. Saloman, Ping Guo, Ting Zhang, Nada Mohamed, Yan Wang, Krishna Prasadan, George K. Gittes

×

Figure 1

Morphological and histological changes in mouse pancreas following chemical pancreatectomy.

Options: View larger image (or click on image) Download as PowerPoint
Morphological and histological changes in mouse pancreas following chemi...
(A) After AcA infusion, gross morphology of the pancreas was abnormally white and edematous at 2 days, translucent with visible islets (arrow) at 2 weeks, and replaced by fatty tissue with visible islets (arrow) at 8 weeks. (B and C) Normal pancreas histology 2 days after saline infusion (B). Two days after AcA infusion, there was exocrine tissue necrosis (asterisks) with intact islets (i). Magnification (inset) of the apparently preserved acinar cells revealed cell swelling and cytoplasmic vacuolization (arrows) (C). (D) Histology of the pancreas after AcA infusion. Intact islets are denoted by i. Arrows denote fat cells at 4 weeks. (E) Immunostaining after AcA infusion showed negative amylase staining (arrows denote amylase remnants at 2 days), with normal insulin and glucagon staining. Illustrative histology results from 5 animals per time point are shown. Scale bars: 200 μm.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts