Insulin resistance in Type 2 (non-insulin-dependent) diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle
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To study whether insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus is due to a defect in the expression of the insulin-responsive glucose transporter gene (GLUT-4) in human skeletal muscle, we measured the level of GLUT-4 mRNA and (in some of the subjects) its protein in muscle biopsies taken from 14 insulin-resistant patients with Type 2 diabetes, 10 first-degree relatives of the diabetic patients and 12 insulin-sensitive control subjects. Insulin sensitivity was measured with a + 45 mU.m2(-1).min-1 euglycaemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. GLUT-4 mRNA was measured using a human GLUT-4 cDNA probe and GLUT-4 protein with a polyclonal antibody specific for the 15 amino acid carboxy-terminal peptide. Both Type 2 diabetic patients and their relatives showed impaired stimulation of total-body glucose disposal by insulin compared with control subjects (29.5 +/- 2.1 and 34.0 +/- 4.8 vs 57.9 +/- 3.1 mumol.kg lean body mass-1.min-1; p less than 0.01). This impairment in glucose disposal was primarily accounted for by a reduction in insulin-stimulated storage of glucose as glycogen (13.0 +/- 2.4 and 15.6 +/- 3.9 vs 36.9 +/- 2.2 mumol.kg lean body mass-1.min-1; p less than 0.01). The levels of GLUT-4 mRNA expressed both per microgram of total RNA and per microgram DNA, were higher in the diabetic patients compared with the control subjects (116 +/- 25 vs 53 +/- 10 pg/microgram RNA and 177 +/- 35 vs 112 +/- 29 pg/microgram DNA; p less than 0.05, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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Muscle tissue from lean and obese type 2 diabetic subjects has normal or increased GLUT4 mRNA expression and normal GLUT4 protein levels, showing that GLUT4 transcriptional and translational regulation is not impaired.
“Muscle tissue from lean and obese type 2 diabetic subjects exhibits normal or increased levels of GLUT4 mRNA expression and normal levels of GLUT4 protein, thus demonstrating that transcriptional and translational regulation of GLUT4 is not impaired [190, 191].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [191]
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- Authors
- Eriksson, J., Koranyi, L., Bourey, R., Schalin-J�ntti, C., Wid�n, E., Mueckler, M., Permutt, A. M., & Groop, L. C.
- Affiliations
- Helsinki University Hospital (FI)
- Washington University in St. Louis (US)
- Venue
- Diabetologia
- Published
- 1992-02
- Volume
- 35
- Issue
- 2
- Pages
- 143-147
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2131031199
- Cited by
- 122
- References
- 33
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- insulin resistance, type 2 diabetes, GLUT4, glucose transporter gene expression, skeletal muscle, glucose disposal, glycogen storage, first-degree relatives, insulin sensitivity, muscle biopsy, gene expression regulation, glucose transporters, IRS-1, insulin receptor substrate 2
- MeSH terms
- Adult, Autoradiography, Blood Glucose, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Insulin, Insulin Resistance, Middle Aged, Monosaccharide Transport Proteins, Muscle Proteins, Muscles, Phosphorus Radioisotopes, Reference Values, RNA, Messenger, Blotting, Western
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