P1469 - Hypophosphatemia Induces Pancreatic Acinar Cell Dysfunction & Primes the Pancreas for Pancreatitis

Husam Mikati, BS¹, Nidula Mullappilly, PhD², Sandip M. Swain, PhD², Joelle M-J Romac, PhD², Rodger Liddle, MD^2
1Duke University School of Medicine, Durham, NC; ²Duke University, Durham, NC

Introduction: Phosphate is critical for many cellular functions, including ATP synthesis. Hypophosphatemia has been observed in many patients with acute pancreatitis, and we previously reported that a low phosphate diet fed to mice triggered alcohol-induced acute pancreatitis. Acinar cells which produce digestive enzymes, compose 90% of the pancreas. Dysregulation of intracellular calcium and insufficient ATP can initiate acute pancreatitis and induce acinar cell necrosis. Here we evaluated the importance of phosphate in regulating intracellular calcium, ATP levels, and exocrine secretion and determined how low phosphate conditions intensify the risk of pancreatitis.

Methods: C57BL/6 mice were fed a normal diet (0.3% phosphate) or a low phosphate diet (0.02% phosphate) for up to three weeks. Live-cell intracellular calcium and ATP levels were measured using calcium dye (calcium 6-QF) and ATP dye (Magnesium-Green), respectively. mRNA levels were quantified using qRT-PCR, and a colorimetric assay was used to measure cholecystokinin-stimulated acinar cell amylase secretion.

Results: The low phosphate diet significantly reduced the serum phosphate levels in mice compared to mice fed a normal diet. Low phosphate conditions increased intracellular basal calcium levels, impaired ATP synthesis, and decreased cholecystokinin-induced amylase secretion in isolated pancreatic acini. We found that low phosphate conditions produced mild pancreatic edema and elevated proinflammatory cytokines in the pancreas.

Discussion: Our results indicate that low phosphate conditions disrupt intracellular calcium homeostasis, reduce ATP levels, impair pancreatic enzyme secretion, and prime the pancreas for alcohol-induced pancreatitis.


Disclosures:


Husam Mikati, BS¹, Nidula Mullappilly, PhD², Sandip M. Swain, PhD², Joelle M-J Romac, PhD², Rodger Liddle, MD². P1469 - Hypophosphatemia Induces Pancreatic Acinar Cell Dysfunction & Primes the Pancreas for Pancreatitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.