Beyond its direct effect on adiponectin production, insulin indirectly ameliorates the biological response to adiponectin by inducing an increase of Adipo R1/R2 receptor expression, principally involved in fatty acid oxidation and glucose uptake, in both physiological and pathophysiological states such as fasting/refeeding, insulin deficiency and hyperinsulinemia, and this occurs via the activation of the insulin/PI3K/FOXO1 pathway [54]. This evidence concerns the gene INS and hyperinsulinism.