SMPD3 and Insulin resistance: Overexpression of Smpd3 in HCC reduced cell proliferation.70In vitro, overexpression of Smpd3 has been shown to promote palmitate-induced insulin resistance.39 Disruption of PI3K/Akt signaling and enhanced stress responses resulting from insulin resistance suggest a potential opposing relationship between Smpd3 and Dtl in the context of WD-induced steatosis.