Collectively, these investigations examined the effects of orexin-A, orexin-B, or their receptors (OX1R and OX2R) on direct indices of glucose homeostasis, such as blood glucose levels, insulin secretion, hepatic glucose production, and GLUT4 translocation, as well as indirect indices, including glucose sensing within orexin neurons and hypoglycemia-triggered arousal or feeding behavior. The gene discussed is INS; the disease is Hypoglycemia.