Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 313; no. 2; pp. R110 - R119
• Main Authors: Kido, Kohei, Yokokawa, Takumi, Ato, Satoru, Sato, Koji, Fujita, Satoshi
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2017
• Subjects: Acetyl-CoA carboxylase; Activation; AKT protein; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Binding Sites; Blood; Blood levels; Effects; Electrical stimuli; Exercise; Gastrocnemius muscle; Gene expression; Glucose; Glucose - metabolism; Impact resistance; Insulin; Insulin - blood; Insulin secretion; Kinases; Male; Muscle, Skeletal - physiology; Muscles; Peroxisome proliferator-activated receptors; Phosphorylation; Phosphorylation - physiology; Physical Conditioning, Animal - methods; Physical Conditioning, Animal - physiology; Protein Binding; Proteins; Rats; Rats, Sprague-Dawley; Resistance Training - methods; Secretion; Signal Transduction - physiology; Skeletal muscle; Strength training; Streptozocin; Toxins; Western blotting; AMPKα Ser485/491; PGC-1α; AMPKα Thr172; resistance exercise; insulin
• ISSN: 0363-6119; 1522-1490; 1522-1490
• DOI: 10.1152/ajpregu.00063.2017

Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPKα Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting β-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPKα Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPKα Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 α (PGC-1α) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPKα Ser485/491 phosphorylation.