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 ^pThr389S6K1 and total S6K1 levels in human and rat fat depots as candidate markers of altered glucose metabolism. ^pThr389S6K1 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. ^pThr389S6K1/_totalS6K1 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 ^pThr389S6K1/totalS6K1 levels in adipose tissue in association with obesity-associated metabolic disturbances. ^pThr389S6K1/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 ^pThr389S6K1/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.