Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schommers, Philipp UNSPECIFIED orcid.org/0000-0003-3375-6800 UNSPECIFIED Thurau, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Bultmann-Mellin, Insa UNSPECIFIED UNSPECIFIED UNSPECIFIED Guschlbauer, Maria UNSPECIFIED orcid.org/0000-0002-5401-4542 UNSPECIFIED Klatt, Andreas R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rozman, Jan UNSPECIFIED orcid.org/0000-0002-8035-8904 UNSPECIFIED Klingenspor, Martin UNSPECIFIED orcid.org/0000-0002-4502-6664 UNSPECIFIED de Angelis, Martin Hrabe UNSPECIFIED orcid.org/0000-0002-7898-2353 UNSPECIFIED Alber, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruendemann, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Sterner-Kock, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language RESPIRATORY-CHAIN; EUROPEAN ASSOCIATION; CONSENSUS STATEMENT; GLUCOSE-METABOLISM; IMAGE-ANALYSIS; INSULIN; WEIGHT; HYPERGLYCEMIA; MANAGEMENT; PHOSPHORYLATION Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22674