Phosphorylated S6K1 (Thr389) is a molecular adipose tissue marker of altered glucose tolerance.
Molecular tissue markers of altered glucose metabolism will be useful as potential targets for antidiabetic drugs. S6K1 is a downstream signal of insulin action. We aimed to evaluate (pThr389)S6K1 and total S6K1 levels in human and rat fat depots as candidate markers of altered glucose metabolism. (pThr389)S6K1 and total S6K1 levels were measured using enzyme linked immune sorbent assay (ELISA) in 49 adipose tissue samples from subjects with morbid obesity and in 18 peri-renal white adipose tissue samples from rats. The effects of high glucose and rosiglitazone have been explored in human preadipocytes. (pThr389)S6K1/(total)S6K1 in subcutaneous adipose tissue was significantly increased subjects with Type 2 diabetes (0.78 ± 0.26 vs. 0.55 ± 0.14, P=.02) and associated with fasting glucose (r=0.46, P=.04) and glycated hemoglobin (r=0.63, P=.02) in SAT. Similar associations with fasting glucose (r=0.43, P=.03) and IRS1 (r=-0.41, P=.04) gene expression were found in visceral adipose tissue. In addition, rat experiments confirmed the higher (pThr389)S6K1/totalS6K1 levels in adipose tissue in association with obesity-associated metabolic disturbances. (pThr389)S6K1/totalS6K1 was validated using western blot in rat adipose tissue. Both ELISA and western blot data significantly correlated (r=0.85, P=.005). In human preadipocytes, high glucose medium led to increased (pThr389)S6K1/total S6K1 levels in comparison with normal glucose medium, which was significantly decreased under rosiglitazone administration. In conclusion, in human and rat adipose tissue, phosphorylated S6K1 is a marker for increased glucose levels.
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBERobn Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III (ISCIII), 17007, Girona, Spain.
José María
JM
Moreno-Navarrete
Francisco
F
Ortega
Miguel Ángel
MÁ
Sánchez-Garrido
Mònica
M
Sabater
Wifredo
W
Ricart
Antonio
A
Zorzano
Manuel
M
Tena-Sempere
José Manuel
JM
Fernández-Real
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D015203:Reproducibility of Results; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism*
D015415:Biomarkers; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013912:Threonine; D019893:Ribosomal Protein S6 Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C526901:Rps6kb1 protein, rat; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1