Stimulation of incretin secretion by dietary lipid: is it dose dependent? Am J Physiol Gastrointest Liver Physiol 2009 Aug;297(2):G299-305
Date
06/13/2009Pubmed ID
19520739Pubmed Central ID
PMC2724086DOI
10.1152/ajpgi.90601.2008Scopus ID
2-s2.0-68049106367 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
After the ingestion of nutrients, secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the enteroendocrine cells increases rapidly. Previous studies have shown that oral ingestion of fat stimulates secretion of both incretins; however, it is unclear whether there is a dose-dependent relationship between the amount of lipid ingested and the secretion of the hormones in vivo. Recently, we found a higher concentration of the incretin hormones in intestinal lymph than in peripheral or portal plasma. We therefore used the lymph fistula rat model to test for a dose-dependent relationship between the secretion of GIP and GLP-1 and dietary lipid. Under isoflurane anesthesia, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single, intraduodenal bolus of saline or varying amounts of the fat emulsion Liposyn II (0.275, 0.55, 1.1, 2.2, and 4.4 kcal). Lymph was continuously collected for 3 h and analyzed for triglyceride, GIP, and GLP-1 content. In response to increasing lipid calories, secretion of triglyceride, GIP, and GLP-1 into lymph increased dose dependently. Interestingly, the response to changes in intraluminal lipid content was greater in GLP-1- than in GIP-secreting cells. The different sensitivities of the two cell types to changes in intestinal lipid support the concept that separate mechanisms may underlie lipid-induced GIP and GLP-1 secretion. Furthermore, we speculate that the increased sensitivity of GLP-1 to intestinal lipid content reflects the hormone's role in the ileal brake reflex. As lipid reaches the distal portion of the gut, GLP-1 is secreted in a dose-dependent manner to reduce intestinal motility and enhance proximal fat absorption.
Author List
Yoder SM, Yang Q, Kindel TL, Tso PAuthor
Tammy Lyn Kindel MD, PhD Associate Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDose-Response Relationship, Drug
Duodenum
Emulsions
Enteroendocrine Cells
Fat Emulsions, Intravenous
Feedback, Physiological
Gastric Inhibitory Polypeptide
Gastrointestinal Motility
Glucagon-Like Peptide 1
Incretins
Intestinal Absorption
Intubation, Gastrointestinal
Lymph
Male
Phospholipids
Rats
Rats, Sprague-Dawley
Safflower Oil
Soybean Oil
Time Factors
Triglycerides
