Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP.

Journal Article (Journal Article)

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins produced in the intestine that play a central role in glucose metabolism and insulin secretion. Circulating concentrations of GLP-1 and GIP are low and can be difficult to assay in rodents. These studies utilized the novel intestinal lymph fistula model we have established to investigate the mechanism of lipid-stimulated incretin secretion. Peak concentrations of GLP-1 and GIP following an enteral lipid stimulus (Liposyn) were significantly higher in intestinal lymph than portal venous plasma. To determine whether lipid-stimulated incretin secretion was related to chylomicron formation Pluronic L-81 (L-81), a surfactant inhibiting chylomicron synthesis, was given concurrently with Liposyn. The presence of L-81 almost completely abolished the increase in lymph triglyceride seen with Liposyn alone (P < 0.001). Inhibition of chylomicron formation with L-81 reduced GLP-1 secretion into lymph compared to Liposyn stimulation alone (P = 0.034). The effect of L-81 relative to Liposyn alone had an even greater effect on GIP secretion, which was completely abolished (P = 0.004). These findings of a dramatic effect of L-81 on lymph levels of GLP-1 and GIP support a strong link between intestinal lipid absorption and incretin secretion. The relative difference in the effect of L-81 on the two incretins provides further support that nutrient-stimulation of GIP and GLP-1 is via distinct mechanisms.

Full Text

Duke Authors

Cited Authors

  • Lu, WJ; Yang, Q; Yang, L; Lee, D; D'Alessio, D; Tso, P

Published Date

  • June 2012

Published In

Volume / Issue

  • 47 / 6

Start / End Page

  • 571 - 580

PubMed ID

  • 22297815

Pubmed Central ID

  • PMC3506258

Electronic International Standard Serial Number (EISSN)

  • 1558-9307

Digital Object Identifier (DOI)

  • 10.1007/s11745-011-3650-1


  • eng

Conference Location

  • United States