S6K1's Role in the Progression of Type 2 Diabetes as It Relates to Age- and Diet- Induced Obesity

Abstract: 

S6 kinase 1 (S6K1) is a protein kinase that is involved in the signal transduction pathway that begins at the activation of an insulin (or similarly related) receptor. S6K1, unlike most effectors of insulin action, is sensitive to nutrients in the body, including glucose and amino acids. This sensitivity to nutrients makes S6K1 an important player in insulin action because insulin-induced metabolic responses are dependent on the nutritional state in the body. Type 2 diabetes is most often linked with obesity, where nutrient levels are continually elevated causing eventual resistance to insulin, so S6K1 has widely been studied to understand why nutrient elevation leads to insulin resistance and ultimately Type 2 diabetes. A research group headed by George Thomas at the Friedrich Miescher Institute for Biomedical Research recently published an article in Nature [1] that showed that mice lacking S6K1 were protected against age- and diet- induced obesity and were protected against insulin resistance (even on a high fat diet). These mice had a higher sensitivity to insulin and higher metabolic rates than normal mice with S6K1. They further showed that S6K1 is a regulator of insulin action, and propose that its constant activation (due to increased nutrient levels associated with obesity) inhibits insulin action, leads to insulin resistance, and eventually causes Type 2 diabetes.

[1] Um, Sung Hee; Frigerio, Francesca; Watanabe, Mitsuhiro; Picard, Frederic; Joaquin, Manel; Sticker, Melanie; Fumagalli, Stefano; Allegrini, Peter R.; Kozma, Sara C.; Auwerx, Johan and Thomas, George (2004); "Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.";  Nature 431: 200-205. [pdf]