Curcumin promotes the inhibition IRS-1 s1101 phosphorylation while restoring insulin signaling and phosphorylation of PRAS 40 and RPS6.

The search for natural compounds that elicit medicinal effects has increased over the years as synthetic compounds often carry adverse side effects. p300, an acetyltransferase protein recently found to negatively impact the insulin signaling pathway when overexpressed, has often been targeted in research using a synthetic compound called C646. However, curcumin, a natural compound, has been shown to also inhibit p300. Curcumin has been theorized as a potential treatment for diabetes, however the connection between its ability to inhibit the excessive expression of p300 seen when consuming a high fat diet and its ability to restore insulin signaling has never been tied together until now. We hypothesize that curcumin inhibits p300 as effectively as C646 does, resulting in a decrease in the phosphorylation of IRS-1 s1101, a posttranslational modification that is enhanced in the presence of p300. We cultured HepG2 cells and starved them before stimulating them with insulin for 30min, then insulin combined with palmitic acid and glucose. The cells were then treated with either C646 or curcumin for 16hrs. Samples were collected and subjected to an SDS PAGE and western blot before they were analyzed. Our results revealed that curcumin effectively reduced the inhibitory s1101 phosphorylation comparable to C646. This positive effect by curcumin was followed by the phosphorylation of down stream targets, PRAS 40 and RPS6, while C464 did not show this similar added outcome. Curcumin’s effect in the insulin pathway is not isolated to increasing Glu 4 expression alone but also preventing the negative regulation of IRS-1 subjected by over expressed p300 which enhances the phosphorylation of s1101 by kinases such as S6K-1. While most metabolic ailments could be deterred by a change in lifestyle, people are not disciplined enough to put in the work and would rather take a drug or supplement. Thus, truly understanding what we are consuming and exactly how it affects our body is essential.