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

Autor: Kalsi RS; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Kreger AM; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Saleh M; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.; Division of Pediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Yoshida S; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Sharma K; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Fusco J; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Saloman JL; Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Zhang T; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Thomas M; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Sehrawat A; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Wang Y; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Reif J; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Mills J; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Raad S; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Zengin B; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Gomez A; Division of Pediatric Pathology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Singhi A; Divisions of Anatomic Pathology and Molecular Genomic Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Tadros S; Department of Pediatric Radiology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Slivka A; Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Esni F; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Prasadan K; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA., Gittes G; Division of Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. George.Gittes@chp.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jun 05; Vol. 13 (1), pp. 9113. Date of Electronic Publication: 2023 Jun 05.
DOI: 10.1038/s41598-023-35820-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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