Given that insulin and glucagon seem to increase alpha-cell proliferation44, the diminished proliferative values observed here may be associated with the lower plasma glucagon levels (Fig. 1A) and are likely related to alpha-cell insulin resistance, as has been suggested to occur in type 2 diabetes45 and after long-term insulin exposure46.The lack of suppression of glucagon release (Fig. 1F) may also be indicative of alpha-cell insulin resistance. Here, INS is linked to Insulin resistance.