Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini

Pancreas. 2024 Sep 1;53(8):e662-e669. doi: 10.1097/MPA.0000000000002350. Epub 2024 May 1.

Abstract

Objectives: Amino acids play an essential role in protein synthesis, metabolism, and survival of pancreatic acini. Adequate nutritional support is important for acute pancreatitis treatment. However, high concentrations of arginine and lysine may induce acute pancreatitis. The study aimed to identify the most suitable l -amino acids as safe energy sources for pancreatic acinar cells.

Materials and methods: Pancreatic acini were isolated from male Wistar rats. Effects of amino acids (0.1-20 mM) on uncoupled respiration of isolated acini were studied with a Clark electrode. Cell death was evaluated with fluorescent microscopy and DNA gel electrophoresis.

Results: Among the tested amino acids, glutamate, glutamine, alanine, lysine, and aspartate were able to stimulate the uncoupled respiration rate of isolated pancreatic acini, whereas arginine, histidine, and asparagine were not. Lysine, arginine, and glutamine (20 mM) caused complete loss of plasma membrane integrity of acinar cells after 24 hours of incubation. Glutamine also caused early (2-4 hours) cell swelling and blebbing. Aspartate, asparagine, and glutamate only moderately decreased the number of viable cells, whereas alanine and histidine were not toxic. DNA fragmentation assay and microscopic analysis of nuclei showed no evidence of apoptosis in cells treated with amino acids.

Conclusions: Alanine and glutamate are safe and effective energy sources for mitochondria of pancreatic acinar cells.

MeSH terms

  • Acinar Cells* / drug effects
  • Acinar Cells* / metabolism
  • Amino Acids* / metabolism
  • Amino Acids* / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Arginine / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Energy Metabolism / drug effects
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Glutamic Acid / toxicity
  • Glutamine / metabolism
  • Glutamine / pharmacology
  • Histidine / pharmacology
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxygen Consumption / drug effects
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Rats
  • Rats, Wistar*

Substances

  • Amino Acids
  • Glutamine
  • Arginine
  • Glutamic Acid
  • Histidine