title: Coingestion of acylglycerols differentially affects glucose-induced insulin secretion via glucose-dependent insulinotropic polypeptide in C57BL/6J mice.
abstract: The precise role of fat in postprandial glycemia and insulinemia has not been thoroughly researched because postprandial blood glucose and concurrent insulin secretion are largely assumed to be proportional to carbohydrate intake. Recent studies have suggested that dietary fat differentially regulates the postprandial insulin response. To explore this, we examined the effects of coadministered fat on glucose-induced glycemia and insulinemia in C57BL/6J mice. The insulin response to glucose was augmented by the addition of glycerol trioleate (TO) in a dose-dependent manner, which was associated with enhanced glucose transport from the circulation to muscle and adipose tissues. To investigate the mechanism underlying fat-induced hyperinsulinemia, we examined the release of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1. TO increased GIP secretion, whereas glucagon-like peptide-1 secretion was unaffected. TO-induced hyperinsulinemia was significantly attenuated by the pretreatment of mice with a specific GIP antagonist. Diacylglycerol (DAG) promoted lower postprandial GIP and triglyceride responses and, when ingested with glucose, a lower insulin response compared with triacylglycerol of a similar fatty acid composition. Pluronic L-81, an inhibitor of chylomicron formation, reduced not only the triglyceride response but also TO-induced GIP secretion, indicating that the lower GIP response after DAG ingestion may be associated with retarded chylomicron formation in the small intestine. We conclude that dietary fat augments glucose-induced insulinemia via gut-derived GIP and, thereby, influences postprandial nutrient metabolism in mice. DAG promotes a lower GIP and thereby reduced insulin responses compared with triacylglycerol, which may differentially influence postprandial energy homeostasis.
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi 321-3497, Japan. shimotoyodome.akira@kao.co.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Shimotoyodome
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukuoka
authors.forename: Junko
authors.initials: J
authors.lastname: Suzuki
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujii
authors.forename: Tomohito
authors.initials: T
authors.lastname: Mizuno
authors.forename: Shinichi
authors.initials: S
authors.lastname: Meguro
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tokimitsu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hase
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004338:Drug Combinations; D004435:Eating / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005989:Glycerides / Q000008:administration & dosage / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D011964:Receptors, Gastrointestinal Hormone; D014018:Tissue Distribution
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D004338:Drug Combinations; D005989:Glycerides; D006727:Hormone Antagonists; D054795:Incretins; D007328:Insulin; D010446:Peptide Fragments; D011964:Receptors, Gastrointestinal Hormone; C120067:glucose-dependent-insulinotropic-polypeptide (7-30)-amide; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose