title: Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding.
abstract: OBJECTIVE
  GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic-hormonal parameters triggered by refeeding upon the Slc2a4 expression.
  
  
  METHODS
  Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2-4h after spontaneous refeeding; ii) 2-4h after T3 injection, without refeeding; and iii) 0.5-2h after intravenous infusion of insulin, insulin+glucose and insulin+amino acids, without refeeding.
  
  
  RESULTS
  Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~20%, P<0.05 vs. fasting), but T3 injection induced a ~2-fold increase in Slc2a4 mRNA, 2-4h later (P<0.001). Moreover, T3 increased glycemia and insulinemia to the 2h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding.
  
  
  CONCLUSIONS
  Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05088-900, Brazil.
authors.forename: Melissa Moreira
authors.initials: MM
authors.lastname: Zanquetta
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05088-900, Brazil.
authors.forename: Ana Barbara
authors.initials: AB
authors.lastname: Alves-Wagner
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05088-900, Brazil. Electronic address: morirc-icb@hotmail.com.
authors.forename: Rosana Cristina
authors.initials: RC
authors.lastname: Mori
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05088-900, Brazil.
authors.forename: Raquel Saldanha
authors.initials: RS
authors.lastname: Campello
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05088-900, Brazil.
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D014284:Triiodothyronine; D005947:Glucose
keywords: Fasting; GLUT4; Insulin resistance mechanism; Skeletal muscle