Importantly, despite apparently promoting hepatic glucose output by increasing the availability of gluconeogenic substrates in the presence of insulin, in conditions in which insulin levels are low, like in T2D, leptin inhibits lipolysis thus decreasing the circulating levels of gluconeogenic substrates such as glycerol, fatty acids, and ketone bodies, which may play a role in suppressing gluconeogenesis under leptin therapy 41. Here, INS is linked to type 2 diabetes mellitus.