Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1
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Aims/hypothesis The aim of this study was to determine the effect of several antidiabetic agents on insulin-stimulated glycogen synthesis, as well as on mRNA expression.Methods Cultured primary human skeletal myotubes obtained from six healthy subjects were treated for 4 or 8 days without or with glucose (25 mmol/l), insulin (400 pmol/l), rosiglitazone (10 micromol/l), metformin (20 micromol/l) or the AMP-activated kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) (200 micromol/l). After this, insulin-stimulated glycogen synthesis was determined. mRNA levels of the glucose transporters GLUT1 and GLUT4, the peroxisomal proliferator activator receptor gamma (PPAR gamma) co-activator 1 (PGC1) and the myocyte-specific enhancer factors (MEF2), MEF2A, MEF2C and MEF2D were determined using real-time PCR analysis after 8 days exposure to the various antidiabetic agents.Results Insulin-stimulated glycogen synthesis was significantly increased in cultured human myotubes treated with insulin, rosiglitazone or metformin for 8 days, compared with non-treated cells. Furthermore, an 8-day exposure of myotubes to 25 mmol/l glucose impaired insulin-stimulated glycogen synthesis. In contrast, treatment with AICAR was without effect on insulin-mediated glycogen synthesis. Exposure to insulin, rosiglitazone or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25 mmol/l glucose treatment increased GLUT1 mRNA expression. Metformin also increased mRNA expression of the MEF2 isoforms.Conclusions/interpretation Enhanced insulin-stimulated glycogen synthesis in human skeletal muscle cell culture coincides with increased GLUT4 and PGC1 mRNA expression following treatment with various antidiabetic agents. These data show that chronic treatment of human myotubes with insulin, metformin or rosiglitazone has a direct positive effect on insulin action and mRNA expression.
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Exposing human primary muscle cells to insulin upregulates the expression of PGC-1α.
“it has been reported that exposing human primary muscle cells to insulin upregulates the expression of PGC-1α (27).”
From Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance (2010) · cites this paper as [27]
Diabetes treatments increase PGC-1α expression and muscular oxidative capacity.
“Treatments that successfully treat diabetes also increase PGC-1α expression [106] and muscular oxidative capacity [107].”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [106]
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- Authors
- Al-Khalili, L., Forsgren, M., Kannisto, K., Zierath, J. R., Lönnqvist, F., & Krook, A.
- Affiliations
- Swedish Orphan Biovitrum (Sweden) (SE)
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Krook, A.
- Venue
- Diabetologia
- Published
- 2005-04-30
- Volume
- 48
- Issue
- 6
- Pages
- 1173-1179
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2005613002
- Cited by
- 78
- References
- 50
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 6
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stiftelsen Forska Utan Djurförsök
- Vetenskapsrådet
- Sveriges Läkarförbund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- metformin, rosiglitazone, GLUT4, GLUT1, PGC-1, skeletal muscle myotubes, antidiabetic drugs, insulin action, AMPK, glucose transporters, type 2 diabetes
- MeSH terms
- Rosiglitazone, Adult, Aminoimidazole Carboxamide, Biopsy, Cells, Cultured, Female, Glucose, Glycogen, Humans, Insulin, Male, Metformin, Middle Aged, Monosaccharide Transport Proteins, Muscle Proteins, Reference Values, Ribonucleotides, RNA, Messenger, Transcription Factors, Muscle, Skeletal, Muscle Fibers, Skeletal, Thiazolidinediones, Glucose Transporter Type 4
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