It was indicated that hyperglycemia was involved with disrupted glucose transport leading to the dysregulation of osmolarity and brain metabolism, greater atrophy of the hippocampus and amygdala with elevating glucose level, dysfunctional glucose regulation eliciting neuronal synaptic reorganization, decreased insulin secretion or action, impairment in the hypothalamic−pituitary−adrenal (HPA) axis, obesity, hyperleptinemia, oxidative stress, and inflammation. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.