Abstract
Diosmin is a nutrient that is widely contained in citrus and that has been indicated to improve glucose metabolism in diabetic disorders. Recently, we demonstrated that diosmin induces β-endorphin to lower hyperglycemia in diabetic rats. However, the mechanisms of diosmin in opioid secretion were unclear. Therefore, we focused on the secretion of opioids from isolated adrenal glands induced by diosmin. The changes in the released β-endorphin-like immunoreactivity (BER) were determined using ELISA. Diosmin increased the BER level in a dose-dependent manner, and this effect was markedly reduced in the absence of calcium ions. Activation of the imidazoline I-2 receptor (I-2R) has been introduced to induce opioid secretion. Interestingly, we observed that diosmin activates CHO cells expressing I-R. Additionally, diosmin-increased BER was inhibited by the blockade of I-2R in isolated adrenal glands. Additionally, an antagonist of I-2R blocked diosmin-induced effects, including the reduction in hyperglycemia and the increase in plasma BER in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated treatment of STZ-diabetic rats with diosmin for one week induced changes in hepatic glycogen, lipid levels, and the expression of phosphoenolpyruvate carboxykinase (PEPCK). Furthermore, an antagonist of I-2R blocked the diosmin-induced changes. Additionally, plasma lipids modified by diosmin were also reversed by the blockade of I-2R in STZ-diabetic rats. Taken together, we suggest that diosmin may activate I-2R to enhance the secretion of β-endorphin from adrenal glands and to influence metabolic homeostasis, resulting in alleviation of blood glucose and lipids in STZ-diabetic rats.
Highlights
Diabetes is a major public health problem throughout the world
The effectiveness of diosmin was significantly reduced in calcium-free medium (Figure 1A), indicating that the BER secretion from adrenal glands induced by diosmin is calcium dependent
We identified the mechanism of I-2 receptor (I-2R) in the effects of diosmin via intraperitoneal injection in STZ-induced diabetic rats (STZ)-diabetic rats, an established type-1 diabetes animal model with intraperitoneal injection in STZ-diabetic rats, an established type-1 diabetes animal model with insulin-deficiency [19]
Summary
Diabetes is a major public health problem throughout the world. The classic symptoms of diabetes include polydipsia, polyuria, polyuria, weight loss, fatigue, irritability, and blurred vision. Available therapies for diabetes include insulin and hypoglycemic agents. The search for more effective and safer hypoglycemic agents is important. Some natural products have been documented to be useful in the treatment of diabetes. A natural flavone glycoside (diosmetin 7-rutinoside; PubChem CID 5281613), is contained mainly in citrus [1] and it shows antihyperglycemic [2] and anticancer effects [3], in addition to anti-inflammatory and antioxidant-like actions [4]. In type-2 diabetic animals, diosmin attenuated hyperglycemia and increased insulin
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