The effect of muraglitazar on adiponectin signalling, mitochondrial function and fat oxidation genes in human skeletal muscle in vivo.
Diabet Med
; 32(5): 657-64, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25484175
ABSTRACT
AIMS:
The molecular mechanisms by which muraglitazar (peroxisome proliferator-activated receptor γ/α agonist) improves insulin sensitivity in Type 2 diabetes mellitus are not fully understood. We hypothesized that muraglitazar would increase expression of 5'-monophosphate-activated protein kinase and genes involved in adiponectin signalling, free fatty acid oxidation and mitochondrial function in skeletal muscle.METHODS:
Sixteen participants with Type 2 diabetes received muraglitazar, 5 mg/day (n = 12) or placebo (n = 4). Before and after 16 weeks, participants had vastus lateralis muscle biopsy followed by 180 min euglycaemic hyperinsulinaemic clamp.RESULTS:
Muraglitazar increased plasma adiponectin (9.0 ± 1.1 to 17.8 ± 1.5 µg/ml, P < 0.05), while no significant change was observed with placebo. After 16 weeks with muraglitazar, fasting plasma glucose declined by 31%, fasting plasma insulin decreased by 44%, insulin-stimulated glucose disposal increased by 81%, HbA1c decreased by 21% and plasma triglyceride decreased by 39% (all P < 0.05). Muraglitazar increased mRNA levels of 5'-monophosphate-activated protein kinase, adiponectin receptor 1, adiponectin receptor 2, peroxisome proliferator-activated receptor gamma coactivator-1 alpha and multiple genes involved in mitochondrial function and fat oxidation. In the placebo group, there were no significant changes in expression of these genes.CONCLUSIONS:
Muraglitazar increases plasma adiponectin, stimulates muscle 5'-monophosphate-activated protein kinase expression and increases expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation. These changes represent important cellular mechanisms by which dual peroxisome proliferator-activated receptor agonists improve skeletal muscle insulin sensitivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
/
Transdução de Sinais
/
Músculo Esquelético
/
Diabetes Mellitus Tipo 2
/
Adiponectina
/
Ácidos Graxos não Esterificados
/
Glicina
/
Mitocôndrias Musculares
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article