ArticleDiabetologia2004
WY-14643 and 9- cis-retinoic acid induce IRS-2/PI 3-kinase signalling pathway and increase glucose transport in human skeletal muscle cells: differential effect in myotubes from healthy subjects and Type 2 diabetic patients.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 17 citations in OpenAlex.
- Variation in the Circulating Levels of Retinoic Acid and Type 2 Diabetes: Relationships with Glycemic Control Indices, Disease Treatment and Complications.Diagnostics (Basel, Switzerland) · 2026Article
- Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.Physiological reports · 2018Article
- Novel roles for insulin receptor (IR) in adipocytes and skeletal muscle cells via new and unexpected substrates.Cellular and molecular life sciences : CMLS · 2013Review
- Specificity of insulin signalling in human skeletal muscle as revealed by small interfering RNA.Diabetologia · 2009Review
- Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells.Diabetologia · 2006Article
- Unwinding Complexities of Diabetic Alzheimer by Potent Novel Molecules.American journal of Alzheimer's disease and other dementiasReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisTo determine the effects of peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor (RXR) agonists on insulin action, we investigated the effects of Wy-14643 and 9- cis-retinoic acid (9- cis-RA) on insulin signalling and glucose uptake in human myotubes.
methodsPrimary cultures of differentiated human skeletal muscle cells, established from healthy subjects and Type 2 diabetic patients, were used to study the effects of Wy-14643 and 9- cis-RA on the expression and activity of proteins involved in the insulin signalling cascade. Glucose transport was assessed by measuring the rate of [(3)H]2-deoxyglucose uptake.
resultsWy-14643 and 9- cis-RA increased IRS-2 and p85alpha phosphatidylinositol 3-kinase (PI 3-kinase) mRNA and protein expression in myotubes from non-diabetic and Type 2 diabetic subjects. This resulted in increased insulin stimulation of protein kinase B phosphorylation and increased glucose uptake in cells from control subjects. Myotubes from diabetic patients displayed marked alterations in the stimulation by insulin of the IRS-1/PI 3-kinase pathway. These alterations were associated with blunted stimulation of glucose transport. Treatment with Wy-14643 and 9- cis-RA did not restore these defects but increased the basal rate of glucose uptake. CONCLUSIONS/
interpretationThese results demonstrate that PPARalpha and RXR agonists can directly affect insulin signalling in human muscle cells. They also indicate that an increase in the IRS-2/PI 3-kinase pathway does not overcome the impaired stimulation of the IRS-1-dependent pathway and does not restore insulin-stimulated glucose uptake in myotubes from Type 2 diabetic patients.
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