Figure 8. Model showing the influence of Zip14 deletion in mice on hepatic zinc and iron metabolism and signaling pathways for glucose homeostasis during endotoxemia.

The influence of the Zip14 null deletion on reduced liver zinc and increased iron uptake is shown. Up-regulation of Zip14 by LPS via toll like receptor 4 (TLR4) in liver and activation of the NFKB pathway leading to increased IL6, for an autocrine response, and from macrophage-produced IL-6. The suppression of IR activation by IL-6 and cAMP-induced SOCSs is also shown. The apparent reduction in glucagon production in pancreatic α cells and the effect on cellular cAMP in the Zip14 KO mice are proposed. We hypothesize that these signaling events produce hypoglycemia by a reduction in gluconeogenesis.