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Diosmin, a Citrus Nutrient, Activates Imidazoline Receptors to Alleviate Blood Glucose and Lipids in Type 1-Like Diabetic Rats

Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung City 90801, Taiwan
Chief Secretary’s Office, Chiayi Hospital, Ministry of Health and Welfare, Chiayi City 60001, Taiwan
Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City 73101, Taiwan
Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City 71101, Taiwan
Authors to whom correspondence should be addressed.
Nutrients 2017, 9(7), 684;
Received: 21 April 2017 / Revised: 26 June 2017 / Accepted: 29 June 2017 / Published: 30 June 2017
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. View Full-Text
Keywords: diosmin; β-endorphin; imidazoline receptor; STZ-diabetic rats diosmin; β-endorphin; imidazoline receptor; STZ-diabetic rats
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Hsu, C.-C.; Lin, M.H.; Cheng, J.-T.; Wu, M.C. Diosmin, a Citrus Nutrient, Activates Imidazoline Receptors to Alleviate Blood Glucose and Lipids in Type 1-Like Diabetic Rats. Nutrients 2017, 9, 684.

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