INS and Hyperglycemia: Finally note, in addition to aPKC activation by PI3K‐dependent increases in PIP3,4, 5, 6 during insulin and other polypeptide action, and by diet‐induced increases in hepatic ceramides and PA, aPKCs are activated by PA produced by (a) de novo synthesis from glycerol‐3‐PO4 and fatty acyl‐CoA; (b) phospholipase D, during ERK activation by hyperglycemia,71 metformin/AICAR,25, 26, 72, 73 and sorbitol/oxidation74; and (c) diglyceride‐kinase‐dependent phosphorylation of DAG produced by phospholipase C, as activated by H2O2,75 lipopolysaccharides,76 and related proinflammatory agents.