Moreover, direct interactions have been reported between G-protein receptors [49, 50] and tyrosine kinase receptors (e.g. insulin receptor) making it tempting to speculate that mild hyperinsulinemia with insulin-sensitizing adiponectin (in obese-prediabetic mice) is sufficient to activate a vasoactive pathway involving CGRP, IR-TK, PI3K, AKT and eNOS to promote normalization PIV response. This evidence concerns the gene INS and hyperinsulinism.