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Endocrinology. 2015 Apr;156(4):1242-50. doi: 10.1210/en.2014-1748. Epub 2015 Jan 16.

γ-Oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) (C.K., S.S., R.U., M.H., H.T., M.S., H.M.), Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; The Diabetes and Life-Style Related Disease Center (M.H.), Tomishiro Central Hospital, Okinawa 901-0243, Japan; Tanaka Clinic (H.T.), Okinawa 901-0244, Japan; Department of Molecular Anatomy (C.S.-O., C.T.), Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; Department of Neurosurgery (S.I.), Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; Department of Molecular and Cellular Physiology (M.M.), Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; Department of Pharmacology (M.T.), Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; Division of Stem Cell Regulation Research (J.-i.M.), Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; Institute for Genome Research (S.O.), University of Tokushima, Tokushima 770-8506, Japan; and Department of Cardio-Diabetes Medicine (M.S.), University of Tokushima Graduate School of Health Biosciences, Tokushima 770-8503, Japan.

Abstract

Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of β-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that γ-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby γ-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells using murine β-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, γ-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2α, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of γ-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of γ-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in β-cells were observed. Also in this model, γ-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that γ-oryzanol directly ameliorates ER stress-induced β-cell dysfunction and subsequent apoptosis, highlighting usefulness of γ-oryzanol for the treatment of diabetes mellitus.

PMID:
25594697
DOI:
10.1210/en.2014-1748
[Indexed for MEDLINE]

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