INS and Insulin resistance: PUGNAc has been shown to decrease insulin-stimulated glucose uptake in cultured 3T3-L1 adipocytes (Vosseller et al., 2002; Yang et al., 2008), muscle tissue studied ex vivo (Arias et al., 2004), as well as primary adipocytes (Park et al., 2005); these studies, which all make use of PUGNAc, have provided a key part of the foundation for the hypothesis that increased O-GlcNAc levels cause insulin resistance.