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Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models
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
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
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Research Article Endocrinology Gastroenterology

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

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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

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Figure 4

Chemical pancreatectomy preserves the ultrastructure of islet capillaries and innervation.

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Chemical pancreatectomy preserves the ultrastructure of islet capillarie...
(A and B) EM of the islet capillary-endocrine cell interface in controls (A) and 6 months after AcA infusion (B). Red arrows denote hormone-containing granules of the islet cells. Yellow arrows denote the intact endothelial fenestrations, characteristic of mature islet vessels. Asterisks denote red blood cells in the capillary lumen. Scale bars: 600 nm (A and B, right panel); 1 μm (B, left panel). (C) Immunostaining for PGP9.5 (arrows) and insulin showed intact neurons in the parenchyma of the AcA-treated pancreata at serial time points. (D) Whole-mount immunostaining for neurons (PGP9.5) and insulin in naive pancreas and 6 months after AcA infusion showed apparently intact nerve endings supplying the islets. Illustrative histology results from 5 animals per time point are shown. For the EM, illustrative data from 3 animals are shown. Scale bars: 200 μm (C and D).

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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