Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP.
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.
Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA. wendell.lu7@gmail.com
Wendell J
WJ
Lu
Qing
Q
Yang
Li
L
Yang
Dana
D
Lee
David
D
D'Alessio
Patrick
P
Tso
D000818:Animals; D002914:Chylomicrons / Q000378:metabolism*; D004655:Emulsions / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D054709:Lecithins / Q000494:pharmacology; D008196:Lymph / Q000378:metabolism / Q000502:physiology; D008297:Male; D011060:Poloxalene / Q000494:pharmacology; D020442:Poloxamer / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000494:pharmacology; D013024:Soybean Oil / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D002914:Chylomicrons; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D054709:Lecithins; D013501:Surface-Active Agents; D014280:Triglycerides; C422648:pluronic block copolymer p85; C031435:safflower oil, soybean oil, lecithin emulsion; D020442:Poloxamer; D005749:Gastric Inhibitory Polypeptide; D013024:Soybean Oil; D012450:Safflower Oil; D052216:Glucagon-Like Peptide 1; D011060:Poloxalene