1. Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway
- Author
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Takashi Miki, Junki Miyamoto, Kenichi Furusawa, Satoshi Uematsu, Xilin Zhang, Ikuo Kimura, Tomoaki Taknaka, Eun Young Lee, Kosuke Fujimoto, and Takahito Jomori
- Subjects
0301 basic medicine ,endocrine system ,medicine.medical_specialty ,1-Deoxynojirimycin ,Endocrinology, Diabetes and Metabolism ,Gastric Inhibitory Polypeptide ,Gut flora ,Incretins ,Receptors, G-Protein-Coupled ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Endocrinology ,KATP Channels ,Glucagon-Like Peptide 1 ,Oral administration ,Internal medicine ,medicine ,Animals ,Glycoside Hydrolase Inhibitors ,Secretion ,Maltose ,Receptor ,biology ,Chemistry ,Miglitol ,Glucose transporter ,Carbohydrate ,Fatty Acids, Volatile ,biology.organism_classification ,Gastrointestinal Microbiome ,030104 developmental biology ,Carbohydrate Metabolism ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Mechanisms of carbohydrate-induced secretion of the two incretins namely glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are considered to be mostly similar. However, we found that mice exhibit opposite secretory responses in response to co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol), stimulatory for GLP-1, as reported previously, but inhibitory for GIP. Gut microbiota was shown to be involved in maltose/miglitol-induced GIP suppression, as the suppression was attenuated in antibiotics (Abs)-treated mice and abolished in germ-free mice. In addition, maltose/miglitol administration increased plasma levels of short-chain fatty acids (SCFAs), carbohydrate-derived metabolites, in the portal vein. GIP suppression by maltose/miglitol was not observed in mice lacking a SCFA receptor Ffar3, but it was normally seen in Ffar2-deficient mice. Similar to maltose/miglitol administration, co-administration of glucose plus a sodium glucose transporter inhibitor phloridzin (glucose/phloridzin) induced GIP suppression, which was again cancelled by Abs treatment. In conclusion, oral administration of carbohydrates with α-glucosidase inhibitors suppresses GIP secretion through a microbiota/SCFA/FFAR3 pathway.
- Published
- 2018
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