In the adrenal gland, α1-ARs activation may increase β-endorphin secretion via the PLC-PKC pathway, which in turn activates peripheral MOR to modify gene expression associated with glucose metabolism, including muscle GLUT 4 and hepatic PEPCK, thereby leading to improved peripheral glucose utilization and decreased hepatic gluconeogenesis for amelioration of severe hyperglycemia in type 1-like diabetes (Figure 1). Here, HSPG2 is linked to diabetes mellitus.