INS and Other metabolic disease: The increase in IR staining in young animals was also in agreement with the enlargement of the CBs in metabolic disease animals (Ribeiro et al., 2013) and patients (Cramer et al., 2014) and with the increase in the number of type I cells in these CBs herein observed and with the increased CSN activity in HFHSu young animals and response to insulin (Cracchiolo et al., 2019), clearly stating that insulin in early stages of metabolic dysfunction contributes to CB dysfunction.