This proposal is supported by in vivo studies demonstrating that liver-specific disruption of the insulin signaling pathway causes a decrease in hepatic FGF21 mRNA abundance during both carbohydrate-fed and starved conditions and that streptozotocin-induced diabetes suppresses the ability of starvation to increase hepatic FGF21 mRNA abundance [49], [50]. Here, FGF21 is linked to diabetes mellitus.