Of note, a study testing the role of metformin in ovarian cancer suggested that the sphingolipid rheostat may be a novel metabolic target of metformin [52], and metformin alleviated inflammation by targeting sphingolipid metabolism through inhibiting sphingosine kinase 1 (SPHK1), an enzyme which converts sphingosine, a product of sphingomyelin, to sphingosine 1-phostpate [52,53]; the latter has been shown to act via stimulation of the sphingosine-1-phosphate receptor-2 to impair insulin signaling and reduce hepatic insulin resistance [54]. The gene discussed is INS; the disease is ovarian carcinoma.