1607-P: FGF1 Induces Glucokinase Upregulation and Increased Lactate Export in Mouse Hepatocytes

Rodent studies performed in Dr. Schwartz's lab showed that a single injection of fibroblast growth factor 1 (FGF1) has glucose-lowering activity in diabetic animals and induces concomitant increases in glucokinase (GCK) activity and plasma lactate (Scarlett, JM, Nat Med, 2016). In addition, in vivo experiments performed by our group demonstrated that hepatic lactate export is a surrogate for GCK activity. The mechanism by which FGF1 exerts these effects at cellular level in hepatocytes is unknown. In this study, we treated C57BL/6 mouse hepatocytes with different concentrations of FGF1 (100, 200, or 400 ng/ml) and evaluated GCK gene expression and lactate export from hepatocytes into the medium after 24 h of treatment. FGF1 increased lactate export with 200 to 400 ng/ml FGF1 increased lactate export by 1.5-fold (P<0.05). FGF1 concentration from 100-400 ng/ml did not change cell proliferation, and 200 to 400 ng/ml FGF1 upregulated the expression of GCK by 2.3 and 3-fold (P<0.05), respectively. Thus, these data provide a possible mechanism by which of FGF1 upregulates GCK and, consequently, increases lactate export by hepatocytes. Disclosure M.Kabir: None. M.Ader: None. N.Thomas: None. E.Seki: Research Support; Nippon Zoki Ltd, Jubilant. R.N.Bergman: Consultant; Lilly, ReCor Medical, Inc., Research Support; AstraZeneca. Funding National Institutes of Health (R01DK027619-33A1)