Schommers, Philipp ORCID: 0000-0003-3375-6800, Thurau, Anna, Bultmann-Mellin, Insa, Guschlbauer, Maria ORCID: 0000-0002-5401-4542, Klatt, Andreas R., Rozman, Jan ORCID: 0000-0002-8035-8904, Klingenspor, Martin ORCID: 0000-0002-4502-6664, de Angelis, Martin Hrabe ORCID: 0000-0002-7898-2353, Alber, Jens, Gruendemann, Dirk, Sterner-Kock, Anja and Wiesner, Rudolf J. (2017). Metformin causes a futile intestinal-hepatic cycle which increases energy expenditure and slows down development of a type 2 diabetes-like state. Mol. Metab., 6 (7). S. 737 - 748. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 2212-8778

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Abstract

Objective: Metformin, the first line drug for treatment of type 2 diabetes, suppresses hepatic gluconeogenesis and reduces body weight in patients, the latter by an unknown mechanism. Methods: Mice on a high fat diet were continuously fed metformin in a therapeutically relevant dose, mimicking a retarded formulation. Results: Feeding metformin in pharmacologically relevant doses to mice on a high fat diet normalized HbA1c levels and ameliorated glucose tolerance, as expected, but also considerably slowed down weight gain. This was due to increased energy expenditure, since food intake was unchanged and locomotor activity was even decreased. Metformin caused lactate accumulation in the intestinal wall and in portal venous blood but not in peripheral blood or the liver. Increased conversion of glucose-1-C-13 to glucose-1,6-C-13 under metformin strongly supports a futile cycle of lactic acid production in the intestinal wall, and usage of the produced lactate for gluconeogenesis in liver. Conclusions: The reported glucose-lactate-glucose cycle is a highly energy consuming process, explaining the beneficial effects of metformin given continuously on the development of a type 2 diabetic-like state in our mice. (C) 2017 The Authors. Published by Elsevier GmbH.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Thurau, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bultmann-Mellin, InsaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guschlbauer, MariaUNSPECIFIEDorcid.org/0000-0002-5401-4542UNSPECIFIED
Klatt, Andreas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rozman, JanUNSPECIFIEDorcid.org/0000-0002-8035-8904UNSPECIFIED
Klingenspor, MartinUNSPECIFIEDorcid.org/0000-0002-4502-6664UNSPECIFIED
de Angelis, Martin HrabeUNSPECIFIEDorcid.org/0000-0002-7898-2353UNSPECIFIED
Alber, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruendemann, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sterner-Kock, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesner, Rudolf J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-226746
DOI: 10.1016/j.molmet.2017.05.002
Journal or Publication Title: Mol. Metab.
Volume: 6
Number: 7
Page Range: S. 737 - 748
Date: 2017
Publisher: ELSEVIER SCIENCE BV
Place of Publication: AMSTERDAM
ISSN: 2212-8778
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RESPIRATORY-CHAIN; EUROPEAN ASSOCIATION; CONSENSUS STATEMENT; GLUCOSE-METABOLISM; IMAGE-ANALYSIS; INSULIN; WEIGHT; HYPERGLYCEMIA; MANAGEMENT; PHOSPHORYLATIONMultiple languages
Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22674

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