Differential regulation of stimulated glucose transport by free fatty acids and PPARα or -δ agonists in cardiac myocytes

Autor: Christophe Albert Montessuit, Corinne Pellieux, Irène Papageorgiou, Mohamed Asrih, René Lerch
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Antimetabolites
Physiology
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Glucose Transport Proteins
Facilitative
Palmitates
Peroxisome proliferator-activated receptor
Stimulation
PPAR alpha/agonists
Fatty Acids
Nonesterified
PPAR agonist
Rats
Sprague-Dawley
Antimetabolites/metabolism
Fatty Acids
Nonesterified/pharmacology
Signal Transduction/drug effects
Insulin
Glucose/metabolism
Myocytes
Cardiac
PPAR delta
Beta oxidation
Cells
Cultured
chemistry.chemical_classification
ddc:616
Microscopy
Confocal
biology
Deoxyglucose/metabolism
Myocytes
Cardiac/drug effects/metabolism
Oxidation-Reduction
Signal Transduction
medicine.medical_specialty
Insulin/pharmacology
Blotting
Western
Biological Transport
Active
Deoxyglucose
Real-Time Polymerase Chain Reaction
Hypoglycemic Agents/pharmacology
Reactive Oxygen Species/metabolism
Physiology (medical)
Internal medicine
medicine
Hypoglycemic Agents
Animals
PPAR alpha
Uncoupling Agents
Glucose transporter
AMPK
Palmitates/metabolism
Oligomycins/pharmacology
Glucose Transport Proteins
Facilitative/biosynthesis/genetics
PPAR delta/agonists
Rats
Insulin receptor
Glucose
Endocrinology
chemistry
biology.protein
Oligomycins
Uncoupling Agents/pharmacology
Reactive Oxygen Species
Biological Transport
Active/drug effects
Zdroj: American Journal of Physiology. Endocrinology and Metabolism, Vol. 302, No 7 (2012) pp. E872-84
ISSN: 0193-1849
Popis: Stimulation of glucose transport in response to insulin or metabolic stress is an important determinant of cardiac myocyte function and survival, particularly during ischemia-reperfusion episodes. The impact of dyslipidemia and its consequence PPAR activation on stimulated glucose transport in cardiac myocytes remains unknown. Isolated adult rat cardiac myocytes were chronically exposed to free fatty acids (FFA) or PPAR agonists. Insulin- (ISGT) and oligomycin-stimulated glucose transport (OSGT) and related cell signaling were analyzed. Exposure of cardiac myocytes to FFA reduced both ISGT and OSGT. Exposure to either PPARα or PPARδ agonists, but not to a PPARγ agonist, reduced ISGT but not OSGT and increased fatty acid oxidation (FAO). The reduction in ISGT was associated with impaired insulin signaling and, in the case of PPAR stimulation, overexpression of SOCS-3, a protein known to hinder proximal insulin signaling. In contrast, the reduction of OSGT could not be explained by a reduced activity of the cellular energy-sensing system, as assessed from the maintained phosphorylation state of AMPK. Inhibition of FAO at the level of mitochondrial acylcarnitine uptake restored OSGT but not ISGT. Seemingly paradoxically, further stimulation of FAO with PPARα or PPARδ agonists also restored OSGT but not ISGT. Together, these results suggest that inhibition of OSGT occurs downstream of energy gauging and is caused by some intermediate(s) of fatty acid oxidation, which does not appear to be acylcarnitines. The results indicate that the mechanisms underlying FFA-mediated inhibition of ISGT and OSGT differ remarkably.
Databáze: OpenAIRE
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