Decreased Transcription of ChREBP-α/β Isoforms in Abdominal Subcutaneous Adipose Tissue of Obese Adolescents With Prediabetes or Early Type 2 Diabetes

Associations With Insulin Resistance and Hyperglycemia

  1. Gerald I. Shulman5,6,7
  1. 1Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut; the
  2. 2Department of Plastic Surgery, Yale University School of Medicine, New Haven, Connecticut; the
  3. 3W.M. Keck Foundation Biostatistics Resource, Yale University School of Medicine, New Haven, Connecticut; the
  4. 4Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; the
  5. 5Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; the
  6. 6Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut; and the
  7. 7Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
  1. Corresponding author: Sonia Caprio, sonia.caprio{at}yale.edu

Abstract

Insulin resistance associated with altered fat partitioning in liver and adipose tissues is a prediabetic condition in obese adolescents. We investigated interactions between glucose tolerance, insulin sensitivity, and the expression of lipogenic genes in abdominal subcutaneous adipose and liver tissue in 53 obese adolescents. Based on their 2-h glucose tests they were stratified in the following groups: group 1, 2-h glucose level <120 mg/dL; group 2, 2-h glucose level between 120 and 140 mg/dL; and group 3, 2-h glucose level >140 mg/dL. Liver and adipose tissue insulin sensitivity were greater in group 1 than in group 2 and group 3, and muscle insulin sensitivity progressively decreased from group 1 to group 3. The expression of the carbohydrate-responsive element-binding protein (ChREBP) was decreased in adipose tissue but increased in the liver (eight subjects) in adolescents with impaired glucose tolerance or type 2 diabetes. The expression of adipose ChREBPα and ChREBPβ was inversely related to 2-h glucose level and positively correlated to insulin sensitivity. Improvement of glucose tolerance in four subjects was associated with an increase of ChREBP/GLUT4 expression in the adipose tissue. In conclusion, early in the development of prediabetes/type 2 diabetes in youth, ChREBPβ expression in adipose tissue predicts insulin resistance and, therefore, might play a role in the regulation of glucose tolerance.

Footnotes

  • Received July 2, 2012.
  • Accepted September 17, 2012.

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  1. Diabetes vol. 62 no. 3 837-844
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