Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.

Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bart Wessels, Jolita Ciapaite, Nicole M A van den Broek, Klaas Nicolay, Jeanine J Prompers
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e6ecce7cfde4841a6cdae3d73e4a2cd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5e6ecce7cfde4841a6cdae3d73e4a2cd
record_format	dspace
spelling	oai:doaj.org-article:5e6ecce7cfde4841a6cdae3d73e4a2cd2021-11-18T08:14:52ZMetformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.1932-620310.1371/journal.pone.0100525https://doaj.org/article/5e6ecce7cfde4841a6cdae3d73e4a2cd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24950069/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pathogenesis of type 2 diabetes. However, its significance for in vivo skeletal muscle mitochondrial function has yet to be elucidated. The aim of this study was to assess the effects of metformin on in vivo and ex vivo skeletal muscle mitochondrial function in a rat model of diabetes. Healthy (fa/+) and diabetic (fa/fa) Zucker diabetic fatty rats were treated by oral gavage with metformin dissolved in water (30, 100 or 300 mg/kg bodyweight/day) or water as a control for 2 weeks. After 2 weeks of treatment, muscle oxidative capacity was assessed in vivo using 31P magnetic resonance spectroscopy and ex vivo by measuring oxygen consumption in isolated mitochondria using high-resolution respirometry. Two weeks of treatment with metformin impaired in vivo muscle oxidative capacity in a dose-dependent manner, both in healthy and diabetic rats. Whereas a dosage of 30 mg/kg/day had no significant effect, in vivo oxidative capacity was 21% and 48% lower after metformin treatment at 100 and 300 mg/kg/day, respectively, independent of genotype. High-resolution respirometry measurements demonstrated a similar dose-dependent effect of metformin on ex vivo mitochondrial function. In conclusion, metformin compromises in vivo and ex vivo muscle oxidative capacity in Zucker diabetic fatty rats in a dose-dependent manner.Bart WesselsJolita CiapaiteNicole M A van den BroekKlaas NicolayJeanine J PrompersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e100525 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bart Wessels Jolita Ciapaite Nicole M A van den Broek Klaas Nicolay Jeanine J Prompers Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
description	Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pathogenesis of type 2 diabetes. However, its significance for in vivo skeletal muscle mitochondrial function has yet to be elucidated. The aim of this study was to assess the effects of metformin on in vivo and ex vivo skeletal muscle mitochondrial function in a rat model of diabetes. Healthy (fa/+) and diabetic (fa/fa) Zucker diabetic fatty rats were treated by oral gavage with metformin dissolved in water (30, 100 or 300 mg/kg bodyweight/day) or water as a control for 2 weeks. After 2 weeks of treatment, muscle oxidative capacity was assessed in vivo using 31P magnetic resonance spectroscopy and ex vivo by measuring oxygen consumption in isolated mitochondria using high-resolution respirometry. Two weeks of treatment with metformin impaired in vivo muscle oxidative capacity in a dose-dependent manner, both in healthy and diabetic rats. Whereas a dosage of 30 mg/kg/day had no significant effect, in vivo oxidative capacity was 21% and 48% lower after metformin treatment at 100 and 300 mg/kg/day, respectively, independent of genotype. High-resolution respirometry measurements demonstrated a similar dose-dependent effect of metformin on ex vivo mitochondrial function. In conclusion, metformin compromises in vivo and ex vivo muscle oxidative capacity in Zucker diabetic fatty rats in a dose-dependent manner.
format	article
author	Bart Wessels Jolita Ciapaite Nicole M A van den Broek Klaas Nicolay Jeanine J Prompers
author_facet	Bart Wessels Jolita Ciapaite Nicole M A van den Broek Klaas Nicolay Jeanine J Prompers
author_sort	Bart Wessels
title	Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
title_short	Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
title_full	Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
title_fullStr	Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
title_full_unstemmed	Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
title_sort	metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/5e6ecce7cfde4841a6cdae3d73e4a2cd
work_keys_str_mv	AT bartwessels metforminimpairsmitochondrialfunctioninskeletalmuscleofbothleananddiabeticratsinadosedependentmanner AT jolitaciapaite metforminimpairsmitochondrialfunctioninskeletalmuscleofbothleananddiabeticratsinadosedependentmanner AT nicolemavandenbroek metforminimpairsmitochondrialfunctioninskeletalmuscleofbothleananddiabeticratsinadosedependentmanner AT klaasnicolay metforminimpairsmitochondrialfunctioninskeletalmuscleofbothleananddiabeticratsinadosedependentmanner AT jeaninejprompers metforminimpairsmitochondrialfunctioninskeletalmuscleofbothleananddiabeticratsinadosedependentmanner
_version_	1718421986425700352

Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.

Ejemplares similares