Mosapride Citrate Increases Postprandial Glucagon-Like Peptide-1, Insulin, and Gene Expression of Sweet Taste Receptors

• Published in: Digestive diseases and sciences 2015-02, Vol.60 (2), p.345-353
• Main Authors: Maruoka, Daisuke, Arai, Makoto, Tanaka, Takeshi, Okimoto, Kenichiro, Oyamada, Arata, Minemura, Shoko, Tsuboi, Masaru, Matsumura, Tomoaki, Nakagawa, Tomoo, Kanda, Tatsuo, Katsuno, Tatsuro, Imazeki, Fumio, Yokosuka, Osamu
• Format: Article
• Language: English
• Subjects: Adult; Animals; Benzamides - administration & dosage; Biochemistry; Diabetics; Drug Administration Schedule; Gastroenterology; Gastrointestinal Agents - administration & dosage; Gene expression; Glucagon; Glucagon-Like Peptide 1 - blood; Glycosylated hemoglobin; Hepatology; Humans; Insulin; Insulin - blood; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Jejunum - drug effects; Jejunum - metabolism; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Morpholines - administration & dosage; Oncology; Original Article; Postprandial Period; Protein binding; Receptors, G-Protein-Coupled - drug effects; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; RNA; RNA, Messenger - metabolism; Taste; Time Factors; Transducin - genetics; Transducin - metabolism; Transplant Surgery; Type 2 diabetes; Up-Regulation
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-014-3271-7

Background and Aim Mosapride citrate—a prokinetic agent—improves hemoglobin A1c levels in diabetic patients; however, the underlying mechanism is unclear. We aimed to clarify this mechanism. Methods Preprandial and postprandial (90 min after a meal) blood was obtained from 12 healthy men, and serum insulin and plasma active glucagon-like peptide-1 concentrations were measured. Measurements were also taken after the administration of 5 mg of mosapride citrate three times per day after every meal for 14 days. In addition, C57BL/6 mice were permitted free access to water containing 0.04 % domperidone (D group) or 0.02 % mosapride citrate (M group) for 2 weeks (four mice per group). T1r2 (taste receptor, type 1, member 2), T1r3 , and Gnat 3 (guanine nucleotide-binding protein, alpha transducing 3) mRNA expression levels of the stomach, duodenum, and proximal and mid-jejunum were evaluated. Results In human subjects, postprandial plasma active glucagon-like peptide-1 and serum insulin concentrations after administration of mosapride citrate were significantly higher than those pre-administration (4.8 ± 2.2 pmol/L, 45.6 ± 41.6 μIU/mL, and 3.7 ± 1.2 pmol/L, 34.1 ± 28.4 μIU/mL, respectively). The mouse expression levels of T1r2 and Gnat3 in the proximal jejunum and mid-jejunum in the M group (4.1 ± 1.8-fold, 3.1 ± 1.6-fold, and 4.6 ± 0.8-fold, 3.1 ± 0.9-fold increases, respectively), were significantly higher than those of the control group. Conclusions The administration of mosapride citrate for 2 weeks enhanced postprandial plasma active glucagon-like peptide-1 and serum insulin concentration and increased the expression of sweet taste receptors in the upper intestine.