Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects with Type 2 Diabetes
Open accessAbstract
Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively. Twelve type 2 diabetic, eight obese, and eight lean subjects exercised on a cycle ergometer for 40 min. Muscle biopsies were done before, during, and after exercise. Subjects underwent this protocol on two occasions, at low (50% Vo(2max)) and moderate (70% Vo(2max)) intensities, with a 4-6 week interval. Exercise had no effect on LKB1 activity. Exercise had a time- and intensity-dependent effect to increase AMPK activity and AS160 phosphorylation. Obese and type 2 diabetic subjects had attenuated exercise-stimulated AMPK activity and AS160 phosphorylation. Type 2 diabetic subjects had reduced basal PGC-1 gene expression but normal exercise-induced increases in PGC-1 expression. Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects.
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IL-6 resistance is characterized by reduced AMPK activity in response to chronic IL-6 exposure.
“This has led to the concept of “IL-6 resistance,” characterized by reduced AMPK activity in response to chronic IL-6 exposure [48].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [48]
The Discussion says IL-6 stimulates muscle AMPK and notes higher IL-6 levels in subjects with type 2 diabetes, but it does not describe chronic IL-6 exposure or define “IL-6 resistance.” The reported blunted AMPK response is to exercise, not to IL-6. Searches for chronic IL-6 exposure and IL-6 resistance found no passage establishing the claimed relationship. (LLM, conf=0.76)
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- Authors
- Sriwijitkamol, A., Coletta, D. K., Wajcberg, E., Balbontin, G. B., Reyna, S. M., Barrientes, J., Eagan, P. A., Jenkinson, C. P., Cersosimo, E., DeFronzo, R. A., Sakamoto, K., & Musi, N.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Texas Diabetes Institute (US)
- Diabetes Division, University of Texas Health Science Center at San Antonio, San Antonio, Texas
- University of Dundee (GB)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-03-01
- Volume
- 56
- Issue
- 3
- Pages
- 836-848
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2844111
- OpenAlex
- W2114452637
- Cited by
- 304
- References
- 63
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 7 · 2022: 13 · 2021: 11 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 16 · 2016: 17 · 2015: 21 · 2014: 19 · 2013: 24 · 2012: 19
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- Funders
- American Diabetes Association (DK24092)
- U.S. Department of Veterans Affairs (DK24092)
- Pfizer
- Endocrine Fellows Foundation (DK24092)
- Mahidol University (DK24092)
- National Institutes of Health (DK24092)
- University of Texas Health Science Center at San Antonio
- Medical Research Council
- Faculty of Medicine Siriraj Hospital, Mahidol University
- National Heart, Lung, and Blood Institute (F32HL086089)
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK024092, DK 067690, DK 24092, R01DK067690, R01DK079195, R01DK024092)
- National Institute on Minority Health and Health Disparities (L60 MD000986)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- AMPK, acute exercise, type 2 diabetes, obesity, skeletal muscle, LKB1, AS160 phosphorylation, PGC-1α, exercise intensity, glucose transport, mitochondrial biogenesis, exercise training
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Adult, Amino Acid Oxidoreductases, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glycogen, Humans, Male, Middle Aged, Multienzyme Complexes, Nucleotides, Obesity, Phosphorylation, Time Factors, Transcription Factors, Signal Transduction, Exercise, Protein Serine-Threonine Kinases, Muscle, Skeletal, GTPase-Activating Proteins, Proto-Oncogene Proteins c-akt, Nuclear Respiratory Factor 1, AMP-Activated Protein Kinases
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