Although the above studies demonstrated a beneficial role of SphK1 on glucose homeostasis and β cell function, another study showed that SphK1 KO mice were protected from HFD-induced glucose intolerance due to a reduced adipocyte pro-inflammatory response, which suggests a negative role of SphK1/S1P axis on regulating glucose homeostasis [78]. The gene discussed is SPHK1; the disease is Glucose intolerance.