Mediation of Endogenous β‐Endorphin in the Plasma Glucose‐Lowering Action of Herbal Products Observed in Type 1‐Like Diabetic Rats

Abstract

Recently, there have been advances in the development of new substances effective in managing diabetic disorders. Opioid receptors couple multiple systems to result in various biological effects, although opioids are best known for analgesia. In the present review, we used our recent data to describe the advance in plasma glucose-lowering action of herbal products, especially the mediation of β-endorphin in glucose homeostasis of insulin-deficient diabetes. In type 1-like streptozotocin-induced diabetic rats, we identified many products purified from herbs that show a dose-dependent plasma glucose-lowering action. Increase in β-endorphin secretion from the adrenal gland may activate peripheral opioid μ-receptors (MOR) to enhance the expression of muscle glucose transporters and/or to reduce hepatic gluconeogenesis at the gene level, thereby leading to improved glucose utilization in peripheral tissues for amelioration of severe hyperglycemia. It has also been observed that stimulation of α 1-adrenoceptors (α 1-ARs) in the adrenal gland by some herbal products is responsible for the increase in β-endorphin secretion via a phospholipase C-protein kinase dependent pathway. However, an increase in β-endorphin secretion from the adrenal gland by herbal products can function via another receptor. New insights into the mediation of endogenous β-endorphin activation of peripheral MOR by herbal products for regulation of glucose homeostasis without the presence of insulin have been established. Therefore, an increase in β-endorphin secretion and/or direct stimulation of peripheral MOR via an insulin-independent action might serve as the potential target for development of a therapeutic agent or promising adjuvant in intensive plasma glucose control.

Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats

“…It has been indicated that opioids secreted from the adrenal gland can lower plasma glucose in STZ‐diabetic rats . Additionally, β‐endorphin is involved in the plasma glucose‐lowering action of herbal products . Therefore, we speculated that the action of diosmin in STZ‐diabetic rats is also associated with β‐endorphin secretion.…”

“…The expression of β‐endorphin binding receptor is elevated in the skeletal muscle of type‐1 and type‐2 diabetic animals . The opioid μ‐receptor is primarily involved in the hypoglycaemic action of natural products in STZ‐diabetic rats . This finding was characterized using opioid μ‐receptor receptor knockout mice .…”

“…In our previous report, β‐endorphin was indicated to be involved in the reduction of hyperglycaemia induced by herbal products including many flavonoids in streptozotocin‐induced diabetic rats (STZ‐diabetic rats), an animal model of type‐1 DM. Exogenous β‐endorphin has been shown to increase circulating insulin in humans with or without DM .…”

Opium and Heroin Alter Biochemical Parameters of Human's Serum

“…In Karam's study, too, FBS was lower in diabetic addicts, but it was not significant (20). Elevated glucose utilization and decrease of hepatic gluconeogenesis due to activation of peripheral opioid µ-receptors (MOR) and modification of glucose metabolismassociated genes have been proposed as the involved mechanisms in decreasing plasma glucose level (21). The effect of morphine on serum level of glucose has been demonstrated on animals (5,8,22,23).…”

Phytotherapy in diabetes: Review on potential mechanistic perspectives

“…Activation of these receptors might enhance the expression of muscle GLUT and/or reduce hepatic gluconeogenesis at the gene level [171] . MOR-induced glucose uptake is accomplished by increased gene expression of GLUT-4 via a phospholipase C-protein kinase (PLC-PKC) dependent pathway [172] . It has also been observed that stimulation of α1-adrenoceptors in the adrenal gland provokes the secretion of β-endorphin [173] depending also on the PLC-PKC pathway [174,175] .…”