Taken together, we posit that the Val mediated intracellular hyperglycemia due to increased basal glucose transport may lead to glucotoxicity, activation of related pathways (i.e., DAG accumulation, AGE formation, and the hexosamine biosynthesis [45]), and subsequent inhibition of insulin signaling by action of TRIB3. The gene discussed is TRIB3; the disease is Hyperglycemia.