GLP-1 stimulates glucose-derived de novo fatty acid synthesis and chain elongation during cell differentiation and insulin release.
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-expressing cells into insulin-releasing beta cells. Here we report stable isotope-based dynamic metabolic profiles of rat pancreatic epithelial (ARIP) and human ductal tumor (PANC-1) cells responding to 10 nM GLP-1 treatment in 48 h cultures. Macromolecule synthesis patterns and substrate flow measurements using gas chromatography/mass spectrometry (MS) and the stable [1,2-13C2]glucose isotope as the tracer 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 the rates of nucleic acid ribose synthesis, glutamate oxidation, or lactate production. Tandem high-performance liquid chromatography-ion trap MS 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.
Bulotta
Angela
A
Division of Endocrinology, Cedars-Sinai Medical Center 8723 Alden Drive, SSB 290 Los Angeles, CA 90048, USA.
Perfetti
Riccardo
R
Hui
Hongxiang
H
Boros
László G
LG
D000818:Animals; D002247:Carbon Isotopes; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats
D002247:Carbon Isotopes; D005227:Fatty Acids; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose