Submitted on February 26, 2003
Revised on May 18, 2003
Accepted on May 19, 2003
Glucagon-like peptide-1 stimulates glucose-derived de novo fatty acid synthesis and chain elongation during cell differentiation and insulin release
Angela Bulotta, Riccardo Perfetti, Hongxiang Hui, and Laszlo G Boros
Pediatrics, University of California at Los Angeles, Torrance, CA 90502
Corresponding Author: boros{at}gcrc.rei.edu
Glucagon-like peptide-1 (GLP-1, 7-36) is capable of restoring normal glucose tolerance in aging, glucose-intolerant Wistar rats and is a potent causal factor in differentiation of human islet duodenal homeobox-1 (PDX-1)-expressing cells into insulin-releasing b cells. Here we report metabolic profiles of rat pancreatic epithelial (ARIP) and human ductal tumor (PANC-1) cells responding to 10nM GLP-1 treatment in 48 h cultures. Macromolecule synthesis patterns and substrate flow measurements using gas chromatography/mass spectrometry and the stable [1,2-13C2]glucose isotope as the single tracer (SIDMAP) showed that GLP-1 induced a significant 20% and 60% increase in de novo fatty acid palmitate synthesis in ARIP and PANC-1 cells, respectively, and it also induced a significant increase in palmitate chain elongation into stearate utilizing glucose as the primary substrate. Distribution of 13C in other metabolites indicated no changes in rates of nucleic acid ribose synthesis, glutamate oxidation or lactate production. Tandem HPLC-ion trap mass spectrometry analysis of the culture media demonstrated mass insulin secretion by GLP-1 treated tumor cells. Metabolic profile changes in response to GLP-1 induced cell differentiation include selective increases in de novo fatty acid synthesis from glucose and consequent chain elongation, allowing increased membrane formation and greater insulin availability and release.
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