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KMID : 1200020200440060908
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Diabetes & Metabolism Journal
2020 Volume.44 No. 6 p.908 ~ p.918
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Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo
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Nepal Mahesh Raj
Kang Mi-Jeong
Kim Geon-Ho
Cha Dong-Ho
Kim Ju-Hyun
Jeong Tae-Cheon
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Abstract
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Background: Voglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo.
Methods: For the in vitro study, different concentrations of voglibose were incubated with intestinal contents, prepared from both vehicle- and antibiotics-treated mice, to determine the decreased amount of voglibose over time by using liquid chromatography-mass spectrometry. Similarly, in vivo pharmacodynamic effect of voglibose was determined following the administration of voglibose and starch in vehicle- and antibiotic-pretreated non-diabetic and diabetic mice, by measuring the modulatory effects of voglibose on blood glucose levels.
Results: The in vitro results indicated that the remaining voglibose could be significantly decreased when incubated with the intestinal contents from normal mice compared to those from antibiotic-treated mice, which had less enzyme activities. The in vivo results showed that the antibiotic pretreatment resulted in reduced metabolism of voglibose. This significantly lowered blood glucose levels in antibiotic-pretreated mice compared to the control animals.
Conclusion: The present results indicate that voglibose would be metabolized by the intestinal microbiota, and that this metabolism might be pharmacodynamically critical in lowering blood glucose levels in mice.
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KEYWORD
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Anti-bacterial agents, Blood glucose, Gastrointestinal microbiome, Metabolism, Voglibose
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