Plasma Glucose Lowering Mechanisms of Catalpol, an Active Principle from Roots of Rehmannia glutinosa, in Streptozotocin-Induced Diabetic Rats

Catalpol is one of the active principles from roots of Rehmannia glutinosa Steud (Scrophulariaceae) that is widely used to treat diabetic disorders in Chinese traditional medicine using the name of Di-Huang, which is used to investigate the mechanisms for lowering of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats). Catalpol decreased plasma glucose in a dose-related manner, and this action was reduced by pretreatment with naloxone or naloxonazine. An increase of plasma beta-endorphin by catalpol was also observed in parallel. The plasma glucose lowering action of catalpol was deleted in bilateral adrenalectomized rats. Moreover, catalpol enhanced beta-endorphin release from the isolated adrenal medulla of STZ-diabetic rats. Otherwise, plasma glucose lowering action of catalpol Failed to produce in opioid mu-receptor knockout mice. Also, repeated administration of catalpol for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal musde. These effects were also reversed by blockade of opioid mu-receptors. Our results suggested that catalpol increased glucose utiliwition through increase of beta-endorphin secretion from adrenal gland in STZ-diabetic rats.