Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance

Figure 2

Pathways to interconnected cellular stresses, stress responses, and stress response dysregulations that contribute to insulin resistance in insulin target cells exposed to excess nutrients (sugars or fatty acids such as palmitate), angiotensin II (Ang II), or bacterial lipopolysaccharide (LPS). ALDR: aldose reductase; AGE: advanced glycation end product; AT₁: angiotensin receptor type 1; DAG: diacylglycerol; DDR: DNA damage response; GS-HNE: glutathione-HNE adduct; GS-HN: glutathionyl-1,4-dihydroxynonene; GSK: glycogen synthase kinase; HSR: heat shock response; IL-1β: interleukin 1β; IL1-R: interleukin 1 receptor; iNOS: inducible nitric oxide synthase; IKK: inhibitor of kappa B kinase; LMP: lysosomal membrane permeabilization; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor kappa B; Nox: NADPH oxidase; PKC: protein kinase C; PLC: phospholipase C; TLR4: toll-like receptor 4; UPP: ubiquitin-proteosome pathway; UPR: unfolded protein response. The stresses, stress responses, and signaling pathways generating them contribute to insulin resistance by multiple mechanisms as described in the text. Insulin resistance may occur because of the combined effects of different components of the system, and these components may promote IR to different extents in different cell types.