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. Author manuscript; available in PMC: 2014 Jan 11.
Published in final edited form as: Science. 2013 Jan 11;339(6116):172–177. doi: 10.1126/science.1230721

Figure 1. Inflammatory signaling pathways link nutrient excess to insulin resistance.

Figure 1

Insulin’s presence at the cell surface is transduced to cytoplasmic and nuclear responses by tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and -2. Serine phosphorylation of these same proteins by Jun N-terminal kinases (JNK) and inhibitor of nuclear factor κB (NF-κB) kinases (IKK), however, potently inhibits insulin signaling. Many diverse cell-intrinsic and -extrinsic sequelae of chronic nutrient excess activate these signaling pathways, directly linking overfeeding to insulin resistance. Furthermore, JNK and IKK activation triggers inflammatory cytokine production, further activating JNK/IKK in an autocrine and paracrine manner and reinforcing insulin resistance. Abbreviations: ER, endoplasmic reticulum; AP-1, activator protein-1.