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Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport
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SYSNO ASEP 0504410 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport Author(s) Horáková, Olga (FGU-C) RID, ORCID
Kroupová, Petra (FGU-C) ORCID
Bardová, Kristina (FGU-C) RID, ORCID, SAI
Burešová, Jana (FGU-C) ORCID, RID
Janovská, Petra (FGU-C) RID, ORCID
Kopecký, Jan (FGU-C) RID, ORCID
Rossmeisl, Martin (FGU-C) RID, ORCIDArticle number 6156 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 9, Apr 16 (2019)Number of pages 11 s. Language eng - English Country GB - United Kingdom Keywords metformin ; blood glucose ; small intestine ; glucose transport ; mice ; AMP-activated protein kinase Subject RIV FB - Endocrinology, Diabetology, Metabolism, Nutrition OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects GA16-08124S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000464652400027 EID SCOPUS 85064569500 DOI 10.1038/s41598-019-42531-0 Annotation Metformin is currently the most prescribed drug for treatment of type 2 diabetes mellitus in humans. It has been well established that long-term treatment with metformin improves glucose tolerance in mice by inhibiting hepatic gluconeogenesis. Interestingly, a single dose of orally administered metformin acutely lowers blood glucose levels, however, little is known about the mechanism involved in this effect. Glucose tolerance, as assessed by the glucose tolerance test, was improved in response to prior oral metformin administration when compared to vehicle-treated mice, irrespective of whether the animals were fed either the standard or high-fat diet. Blood glucose-lowering effects of acutely administered metformin were also observed in mice lacking functional AMP-activated protein kinase, and were independent of g lucagon-like-peptide-1 or N-methyl-D-aspartate receptors signaling. [F-18]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration. Finally, metformin in a dose-dependent but indirect manner decreased glucose transport from the intestinal lumen into the blood, which was observed ex vivo as well as in vivo. Our results support the view that the inhibition of transepithelial glucose transport in the intestine is responsible for lowering blood glucose levels during an early response to oral administration of metformin. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2020 Electronic address https://doi.org/10.1038/s41598-019-42531-0
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