MC4R and hyperinsulinism: Moreover, Morgan et al. (14) demonstrated that MC4R signaling differentially regulates a set of different physiological functions and glucose homeostasis regardless of energy balance, as evidenced also by data on animal models where the deletion of Mc4r gene in both sympathetic and parasympathetic cholinergic neurons impaired glucose homeostasis, leading to hyperinsulinemia and modest insulin resistance (40, 41).