Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function.

Abstract

Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays.  Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.

• Authors: Ranjeet S Kalsi, Alexander M Kreger, Mohamed Saleh, Shiho Yoshida, Kartikeya Sharma, Joseph Fusco, Jami L Saloman, Ting Zhang, Madison Thomas, Anuradha Sehrawat, Yan Wang, Jason Reif, Juliana Mills, Sarah Raad, Bugra Zengin, Ana Gomez, Aatur Singhi, Sameh Tadros, Adam Slivka, Farzad Esni, Krishna Prasadan, George Gittes
• Journal: Research square (Res Sq) (Mar 08 2023) United States
• PMID: 36945494 (Publication Type: Preprint)