INS and hyperinsulinism: Therefore, under physiological conditions such as after a meal, the liver is the main organ involved in insulin clearance and is exposed to ∼3-fold higher insulin levels than peripheral tissues; this ensures the direct and indirect (through inhibition of adipose tissue, lipolysis, and NEFA release) suppression of EGP by insulin and the increase in muscle glucose disposal, avoiding peripheral hyperinsulinemia and the risk of adverse effects (137, 138).