title: The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice.
abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [(14)C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [(14)C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hamasaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Fukuda
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tsukiyama
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010477:Perfusion; D018027:Receptors, Glucagon / Q000235:genetics; D013004:Somatostatin / Q000494:pharmacology
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose