Absence of Insulin Receptor Substrate-1 Expression Does Not Alter GLUT1 or GLUT4 Abundance or Contraction-Stimulated Glucose Uptake by Mouse Skeletal Muscle
Abstract
The purpose of this study was to determine the influence of insulin receptor substrate-1 (IRS-1) expression on GLUT1 and GLUT4 glucose transporter protein abundance, contraction-stimulated glucose uptake, and contraction-induced glycogen depletion by skeletal muscle. Mice (6 months old) from three genotypes were studied: wild-type (IRS-1(+/+)), heterozygous (IRS-1(+/-)) for the null allele, and IRS-1 knockouts (IRS-1(-/-)) lacking a functional IRS-1 gene. In situ muscle contraction was induced (electrical stimulation of sciatic nerve) in one hindlimb using contralateral muscles as controls. Soleus and extensor digitorum longus were dissected and 2-deoxyglucose uptake was measured in vitro. 2-Deoxyglucose uptake was higher in basal muscles (no contractions) from IRS-1(-/-) vs. both other genotypes. Contraction-stimulated 2-deoxyglucose uptake and glycogen depletion did not differ among genotypes. Muscle IRS-1 protein was undetectable for IRS-1(-/-) mice, and values were approximately 40 % lower in IRS-1(+/-) than in IRS-1(+/+) mice. No difference was found in IRS-1(+/+) compared to IRS-1(-/-) groups regarding muscle abundance of GLUT1 and GLUT4. Substantial reduction or elimination of IRS-1 did not alter the hallmark effects of contractions on muscle carbohydrate metabolism--activation of glucose uptake and glycogen depletion.
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Knockout of IRS1 and Akt2 does not affect contraction-mediated glucose uptake.
“2) Knockout of the predominant insulin signaling proteins IRS1 and Akt2 does not affect contraction-mediated glucose uptake [107,108].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [107]
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Loyd, C. (2014) · OhioLink ETD Center (Ohio Library and Information Network)
- Authors
- Dumke, C. L., Wetter, A. C., Arias, E. B., Kahn, C. R., & Cartee, G. D.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Hormone and Metabolic Research
- Publisher
- Georg Thieme Verlag KG
- Published
- 2001-12
- Volume
- 33
- Issue
- 12
- Pages
- 696-700
- ISSN
- 0018-5043 (ISSN-L)
- 1439-4286
- OpenAlex
- W2036370991
- Cited by
- 7
- References
- 0
- Citations by year
- 2019: 1 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone and Metabolic Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 10026)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 33201, R01DK033201)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- IRS-1, GLUT1, GLUT4, glucose transporters, skeletal muscle, glycogen depletion, insulin signaling, soleus muscle, extensor digitorum longus
- MeSH terms
- Animals, Body Weight, Deoxyglucose, Electric Stimulation, Female, Glycogen, Male, Mice, Inbred C57BL, Monosaccharide Transport Proteins, Muscle Contraction, Muscle Proteins, Organ Size, Phosphoproteins, Sciatic Nerve, Mice, Knockout, Muscle, Skeletal, Glucose Transporter Type 1, Glucose Transporter Type 4, Mice, Insulin Receptor Substrate Proteins
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