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

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Abstract

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 Gnat3 (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.

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Abbreviations

BMI:

Body mass index

ER:

Endoplasmic reticulum

GLP-1:

Glucagon-like peptide-1

GNAT3:

Guanine nucleotide-binding protein, alpha transducing 3

t1/2 :

Half-life

HbA1c:

Hemoglobin A1c

IP3:

Inositol 1,4,5-triphosphate

IP3R3:

Inositol 1,4,5-triphosphate receptor type 3

PLCβ2:

Phospholipase Cβ2

RT-PCR:

Reverse transcription PCR

T1R2:

Taste receptor, type 1, member 2

T1R3:

Taste receptor, type 1, member 3

TRPM5:

Transient receptor potential channel 5

VGCC:

Voltage-gated calcium channel

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Authors and Affiliations

  1. Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-Ku, Chiba City, 260-8670, Japan

    Daisuke Maruoka, Makoto Arai, Kenichiro Okimoto, Arata Oyamada, Shoko Minemura, Masaru Tsuboi, Tomoaki Matsumura, Tomoo Nakagawa, Tatsuo Kanda, Tatsuro Katsuno, Fumio Imazeki & Osamu Yokosuka

  2. Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba City, Japan

    Takeshi Tanaka

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  1. Daisuke Maruoka
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Maruoka, D., Arai, M., Tanaka, T. et al. Mosapride Citrate Increases Postprandial Glucagon-Like Peptide-1, Insulin, and Gene Expression of Sweet Taste Receptors. Dig Dis Sci 60, 345–353 (2015). https://doi.org/10.1007/s10620-014-3271-7

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  • DOI: https://doi.org/10.1007/s10620-014-3271-7

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