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J Food Drug Anal. 2019 Jan;27(1):266-274. doi: 10.1016/j.jfda.2018.06.012. Epub 2018 Aug 14.

Rubiscolin-6 activates opioid receptors to enhance glucose uptake in skeletal muscle.

Author information

1
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.
2
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
3
Department of Orthodontics and Dentofacial Orthopedics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
4
Faculty of Public Health, Sam Ratulangi University, Manado, Indonesia.
5
Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
6
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Electronic address: inui@m.kufm.kagoshima-u.ac.jp.

Abstract

Rubiscolin-6 is an opioid peptide derived from plant ribulose bisphosphate carboxylase/oxygenase (Rubisco). It has been demonstrated that opioid receptors could control glucose homeostasis in skeletal muscle independent of insulin action. Therefore, Rubiscolin-6 may be involved in the control of glucose metabolism. In the present study, we investigated the effect of rubiscolin-6 on glucose uptake in skeletal muscle. Rubiscolin-6-induced glucose uptake was measured using the fluorescent indicator 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose (2-NBDG) in L6 and C2C12 cell lines. The protein expressions of glucose transporter 4 (GLUT4) and AMP-activated protein kinase (AMPK) in L6 cells were observed by Western blotting. The in vivo effects of rubiscolin-6 were characterized in streptozotocin (STZ)-induced diabetic rats. Rubiscolin-6 induced a concentration-dependent increase in glucose uptake levels. The increase of phospho-AMPK (pAMPK) and GLUT4 expressions were also observed in L6 and C2C12 cells. Effects of rubiscolin-6 were blocked by opioid receptor antagonists and/or associated signals inhibitors. Moreover, Rubiscolin-6 produced a dose-dependent reduction of blood glucose and increased GLUT4 expression in STZ-induced diabetic rats. In conclusion, rubiscolin-6 increases glucose uptake, potentially via an activation of AMPK to enhance GLUT4 translocation after binding to opioid receptors in skeletal muscle.

KEYWORDS:

AMPK; GLUT4; Glucose uptake; Opioid receptor; Rubiscolin-6

PMID:
30648580
DOI:
10.1016/j.jfda.2018.06.012
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