Preprint Article Version 1 This version is not peer-reviewed

Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo

Version 1 : Received: 21 May 2019 / Approved: 22 May 2019 / Online: 22 May 2019 (12:01:09 CEST)

How to cite: Nepal, M.; Kang, M.J.; Kim, G.H.; Cha, D.H.; Kim, J.S.; Kim, J.H.; Jeong, T.C. Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo. Preprints 2019, 2019050276 Nepal, M.; Kang, M.J.; Kim, G.H.; Cha, D.H.; Kim, J.S.; Kim, J.H.; Jeong, T.C. Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo. Preprints 2019, 2019050276

Abstract

Voglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies proved that none or very less metabolism of voglibose occurred in liver due to its poor intestinal absorption. Trillions of microorganisms reside in intestine and have several roles in metabolism and detoxification of a variety of xenobiotics. Due to the limited information on the metabolism in intestine, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo. 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 disappearance of voglibose over the time by using LC-MS/MS. The results indicated that the remained voglibose could be significantly more reduced when incubated with the intestinal contents from normal mice than with those from antibiotics-treated mice that had less enzyme activities. 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. The results showed that the antibiotic pretreatment to mice resulting in the reduced metabolism of voglibose caused significantly lowered blood glucose levels than control animals. Taken together, the present results clearly indicated that voglibose could be metabolized by intestinal microbiota, and that the metabolism of voglibose by intestinal microbiota would be pharmacodynamically critical in lowering blood glucose level.

Subject Areas

gut microbiota; voglibose; antibiotics; blood glucose; metabolism

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