FIGURE 8.

Schematic illustration of effects of carrageenan on insulin signaling, mediated through GRB10 and inflammation. When inflammation is present, phospho-IκB kinase β leads to phosphorylation of Ser³⁰⁷ of IRS1, an inhibitor of insulin signaling. This leads to decline in Ser(P)⁴⁷³-AKT, with an associated decline in Ser(P)⁴⁰¹-GATA2, an increase in nuclear GATA2, and an increase in mRNA expression of GRB10. The increase in GRB10 affects the downstream insulin signaling because of binding of GRB10 with the IR, leading to inhibition of tyrosine phosphorylation of IRS-1. Hence, feedback is initiated that leads to upstream inhibition of propagation of insulin signals and further insulin resistance when Ser(P)⁴⁷³-AKT is reduced by inflammation. AKT, protein kinase B; CGN, carrageenan; GRB, growth factor receptor-bound protein; Hsp, heat shock protein; IKK, IκB kinase; IRS, insulin receptor substrate; ROS, reactive oxygen species; ub, ubiquitin.