Stimulation of incretin secretion by dietary lipid: is it dose dependent?
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.
Yoder
Stephanie M
SM
University of Cincinnati, Department of Pathology and Laboratory Medicine, ML 0507, Cincinnati, OH 45237, USA. yodersy@email.uc.edu
Yang
Qing
Q
Kindel
Tammy L
TL
Tso
Patrick
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004655:Emulsions; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage* / Q000378:metabolism; D025461:Feedback, Physiological; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D054795:Incretins / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007441:Intubation, Gastrointestinal; D008196:Lymph / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010743:Phospholipids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil; D013024:Soybean Oil; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D054795:Incretins; D010743:Phospholipids; D014280:Triglycerides; C063336:safflower oil, soybean oil, phospholipid emulsion; D005749:Gastric Inhibitory Polypeptide; D013024:Soybean Oil; D012450:Safflower Oil; D052216:Glucagon-Like Peptide 1