However, the possibility that the TRIB3 Q84R variant does not affect human cardiomyocytes is unlikely on light of the findings that studies in primary human endothelial cells [30, 31] and in isolated human pancreatic islets naturally carrying the TRIB3 Q84R variant, as well as in human hepatoma cells transfected with and expressing the TRIB3 Q84R variant [41] have very consistently reported that TRIB3 R84 acts as a gain-of-function variant that alters insulin signaling, and, consequently, cellular specific insulin actions. This evidence concerns the gene TRIB3 and hepatocellular carcinoma.