Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells.

Abstract

AIMS/HYPOTHESIS:

Recent studies have suggested resveratrol (RSV) as a new natural therapeutic agent to treat type 2 diabetes and lipid-induced insulin resistance. Here, we investigated whether RSV could reverse palmitate-induced insulin resistance in human primary muscle cells.

METHODS:

Myotubes obtained from six healthy men (54 ± 3 years (mean ± SE), BMI 25.0 ± 1.7 kg/m(2), fasting plasma glucose concentration (fP-glucose) 5.47 ± 0.09 mmol/l) were treated for 4 h with 100 μmol/l RSV and/or 0.2 mmol/l palmitate, and stimulated with or without 100 nmol/l insulin. Assays of glucose uptake, glycogen synthesis, palmitate oxidation, intracellular signalling and AMP-activated protein kinase (AMPK) activity were performed.

RESULTS:

RSV did not reverse palmitate-induced impairment of glucose metabolism. Surprisingly, RSV decreased glucose uptake and glycogen synthesis in human skeletal muscle cells. Palmitate oxidation and phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase β (ACCβ) were inhibited by RSV, and RSV completely blocked the activity of AMPK isoform complexes α1/β2/γ1 and α2/β2/γ1 in in-vitro kinase activity assays. Endoplasmic reticulum (ER) stress was increased in response to RSV, as indicated by increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) and increased expression of CCAAT/enhancer binding protein homologous protein (CHOP).

CONCLUSIONS/INTERPRETATION:

Acute exposure to RSV inhibits AMPK activity, fatty-acid oxidation and glucose metabolism in human myotubes.

• Authors: P Skrobuk, S von Kraemer, M M Semenova, A Zitting, H A Koistinen
• Journal: Diabetologia (Diabetologia) Vol. 55 Issue 11 Pg. 3051-60 (Nov 2012) ISSN: 1432-0428 [Electronic] Germany
• PMID: 22898769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Palmitates
• Stilbenes
• Glycogen
• AMP-Activated Protein Kinases
• Glucose
• Resveratrol

Topics

• AMP-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Cell Differentiation (drug effects, physiology)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Glucose (pharmacokinetics)
• Glycogen (biosynthesis)
• Humans
• Insulin Resistance (physiology)
• Male
• Middle Aged
• Muscle Fibers, Skeletal (cytology, drug effects, enzymology)
• Palmitates (metabolism, pharmacology)
• Phosphorylation (drug effects, physiology)
• Primary Cell Culture
• Resveratrol
• Signal Transduction (drug effects, physiology)
• Stilbenes (pharmacology)