Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.

Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for dia...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jonas M Kristensen, Steen Larsen, Jørn W Helge, Flemming Dela, Jørgen F P Wojtaszewski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/265ff3b51ed54a058260c1dd9026c6fd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:265ff3b51ed54a058260c1dd9026c6fd
record_format	dspace
spelling	oai:doaj.org-article:265ff3b51ed54a058260c1dd9026c6fd2021-11-18T08:01:39ZTwo weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.1932-620310.1371/journal.pone.0053533https://doaj.org/article/265ff3b51ed54a058260c1dd9026c6fd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341947/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.Jonas M KristensenSteen LarsenJørn W HelgeFlemming DelaJørgen F P WojtaszewskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53533 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonas M Kristensen Steen Larsen Jørn W Helge Flemming Dela Jørgen F P Wojtaszewski Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
description	Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.
format	article
author	Jonas M Kristensen Steen Larsen Jørn W Helge Flemming Dela Jørgen F P Wojtaszewski
author_facet	Jonas M Kristensen Steen Larsen Jørn W Helge Flemming Dela Jørgen F P Wojtaszewski
author_sort	Jonas M Kristensen
title	Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
title_short	Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
title_full	Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
title_fullStr	Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
title_full_unstemmed	Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
title_sort	two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of ampk kinase dead but not wild type mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/265ff3b51ed54a058260c1dd9026c6fd
work_keys_str_mv	AT jonasmkristensen twoweeksofmetformintreatmentenhancesmitochondrialrespirationinskeletalmuscleofampkkinasedeadbutnotwildtypemice AT steenlarsen twoweeksofmetformintreatmentenhancesmitochondrialrespirationinskeletalmuscleofampkkinasedeadbutnotwildtypemice AT jørnwhelge twoweeksofmetformintreatmentenhancesmitochondrialrespirationinskeletalmuscleofampkkinasedeadbutnotwildtypemice AT flemmingdela twoweeksofmetformintreatmentenhancesmitochondrialrespirationinskeletalmuscleofampkkinasedeadbutnotwildtypemice AT jørgenfpwojtaszewski twoweeksofmetformintreatmentenhancesmitochondrialrespirationinskeletalmuscleofampkkinasedeadbutnotwildtypemice
_version_	1718422593254457344

Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.

Ejemplares similares