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

Lipids. 2012 Jun;47(6):571-80. doi: 10.1007/s11745-011-3650-1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chylomicrons / metabolism*
  • Emulsions / pharmacology
  • Fatty Acids, Nonesterified / metabolism
  • Gastric Inhibitory Polypeptide / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Lecithins / pharmacology
  • Lymph / metabolism
  • Lymph / physiology
  • Male
  • Poloxalene / pharmacology
  • Poloxamer / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Safflower Oil / pharmacology
  • Soybean Oil / pharmacology
  • Surface-Active Agents / pharmacology
  • Triglycerides / metabolism

Substances

  • Chylomicrons
  • Emulsions
  • Fatty Acids, Nonesterified
  • Lecithins
  • Surface-Active Agents
  • Triglycerides
  • pluronic block copolymer p85
  • safflower oil, soybean oil, lecithin emulsion
  • Poloxamer
  • Gastric Inhibitory Polypeptide
  • Soybean Oil
  • Safflower Oil
  • Glucagon-Like Peptide 1
  • Poloxalene