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 (original) (raw)

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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·\({\text{m}}^{{\text{2}}^{{\text{ - 1}}} } \)·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 carboxyterminal 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 μmol·kg lean body mass−1·min−1; p<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 μmol·kg lean body mass−1·min−1; p<0.01). The levels of GLUT-4 mRNA expressed both per μg of total RNA and per μg DNA, were higher in the diabetic patients compared with the control subjects (116±25 vs 53±10 pg/μg RNA and 177±35 vs 112±29 pg/μg DNA; p<0.05, p<0.01, respectively). The GLUT-4 mRNA levels in the relatives were not significantly different from that observed in the control subjects (90±16 pg/μg RNA and 117±23 pg/μg DNA; p = NS). The GLUT-4 protein levels did not significantly differ between control subjects, diabetic patients and relatives (494±85, 567±133 and 323±80 cpm/100 μg protein). No correlation was observed between the level of GLUT-4 mRNA andits protein. However, the level of GLUT-4 mRNA and the rate of total-body glucose disposal correlated positively in the control group and in the relatives (both p<0.05) but not in the diabetic subjects. A positive correlation between the level of GLUT-4 protein and total-body glucose disposal was also observed in the control subjects (r = 0.759; p<0.05) and in the relatives (r = 0.794; p<0.01) but not in the diabetic subjects. We conclude that insulin resistance in Type 2 diabetes is not related to a defect in the expression of the GLUT-4 gene in skeletal muscle. Nevertheless, the levels of GLUT-4 mRNA and GLUT-4 protein are related to the rate of total-body glucose disposal in subjects with normal fasting glucose concentrations.

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Authors and Affiliations

1. Fourth Department of Medicine and Department of Biochemistry, Helsinki University Hospital, Helsinki, Finland
   J. Eriksson, C. Schalin-Jäntti, E. Widén & L. C. Groop
2. Metabolism Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
   L. Koranyi, R. Bourey & A. M. Permutt
3. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA
   M. Mueckler

Authors

1. J. Eriksson
2. L. Koranyi
3. R. Bourey
4. C. Schalin-Jäntti
5. E. Widén
6. M. Mueckler
7. A. M. Permutt
8. L. C. Groop

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Eriksson, J., Koranyi, L., Bourey, R. et al. 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.Diabetologia 35, 143–147 (1992). https://doi.org/10.1007/BF00402546

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• Received: 20 December 1990
• Revised: 30 September 1991
• Issue date: February 1992
• DOI: https://doi.org/10.1007/BF00402546

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