Journal of Diabetes & Metabolism

Journal of Diabetes & Metabolism
Open Access

ISSN: 2155-6156

+44 1477412632


S6 Kinase 2 Deficiency Improves Glucose Disposal in Mice Fed a High Fat Diet

Kristin M Taylor, Jeffrey Bajko, Mario S Cabrera, Cliff Kremer, Birgit Meyer-Puttlitz, Anke M Schulte, Seng H Cheng, Ronald K Scheule and Rodney J Moreland

The mammalian target of rapamycin complex 1 (mTORC1) regulates insulin-mediated glucose metabolism, cell proliferation, the oxidative branch of the pentose phosphate pathway, de novo lipogenesis, and autophagy. Ribosomal S6 kinase 1 (S6K1) and 2 (S6K2) are downstream effectors of mTORC1. To characterize the role of S6K2 in insulin-mediated metabolism, the response of S6K2 deficient mice (S6K2-/-) to a glucose challenge was compared to that of wild-type (C57BL/6) and diabetes resistant strains (BALB/c and A/J) after 35 weeks on a high fat diet (HFD). Although S6K2-/- mice fed a HFD gained as much weight as the wild-type C57BL/6 control mice, unlike the wild-type mice they remained glucose tolerant, insulin sensitive, and had lower basal blood glucose levels. Moreover, unlike S6K1 deficient mice, S6K2-/- mice have increased basal plasma insulin levels and increased β-cell mass compared to C57BL/6, BALB/c, and A/J mice. Administration of insulin to S6K2-/- and C57BL/6 mice fed a Standard Diet (SD) resulted in phosphorylation of Ser307 on skeletal muscle Insulin Receptor Substrate 1 (IRS-1); however, when both strains were fed a HFD, phosphorylation of IRS-1 Ser307 was maintained in S6K2-/- mice but inhibited in C57BL/6 mice. Taken together, these results suggest that S6K2 inhibition may represent a strategy for treating type 2 diabetes.