A novel insulinotropic mechanism of whole grain‐derived γ‐oryzanol via the suppression of local dopamine D₂ receptor signalling in mouse islet

Abstract

BACKGROUND AND PURPOSEγ-Oryzanol, derived from unrefined rice, attenuated the preference for dietary fat in mice, by decreasing hypothalamic endoplasmic reticulum stress. However, no peripheral mechanisms, whereby γ-oryzanol could ameliorate glucose dyshomeostasis were explored. Dopamine D2 receptor signalling locally attenuates insulin secretion in pancreatic islets, presumably via decreased levels of intracellular cAMP. We therefore hypothesized that γ-oryzanol would improve high-fat diet (HFD)-induced dysfunction of islets through the suppression of local D2 receptor signalling. EXPERIMENTAL APPROACHGlucose metabolism and regulation of molecules involved in D2 receptor signalling in pancreatic islets were investigated in male C57BL/6J mice, fed HFD and treated with γ-oryzanol . In isolated murine islets and the beta cell line, MIN6 , the effects of γ-oryzanol on glucose-stimulated insulin secretion (GSIS) was analysed using siRNA for D2 receptors and a variety of compounds which alter D2 receptor signalling. KEY RESULTSIn islets, γ-oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D2 receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by γ-oryzanol. Experiments with siRNA for D2 receptors and D2 receptor ligands in vitro suggest that γ-oryzanol suppressed D2 receptor signalling and augmented GSIS. CONCLUSIONS AND IMPLICATIONSγ-Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of γ-oryzanol on D2 receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy. Abbreviations[Ca 2+

Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice

“…Although g-oryzanol has a wide variety of beneficially metabolic effects (Kozuka et al, 2012;Kozuka et al, 2013;Kozuka et al, 2015a, Kozuka et al, 2015b, extremely low absorption efficiency from intestine of g-oryzanol is a tough obstacle for the clinical application. Gamma-oryzanol ameliorates preference for animal fat and fuel metabolism in HFD-fed mice (Kozuka et al, 2012(Kozuka et al, , 2013(Kozuka et al, , 2015a(Kozuka et al, , 2015b. However, in ob/ob mice, the bestknown severest diabetic model in mice, g-oryzanol actually shows no apparent effect on metabolic amelioration.…”

Brown rice‐specific γ‐oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

“…First, c-oryzanol functions as a chaperone and alleviates the exaggerated ER stress in pancreatic islets ( Figure 3) 18 . Second, at both transcription and translation levels, c-oryzanol inhibits the dopamine type 2 receptor (D2R) signaling in pancreatic islets, which is augmented by animal fat-rich diets 19 .…”

Food functionality research as a new national project in special reference to improvement of cognitive and locomotive abilities

“…Clarification of the brain activation functions of common food factors are extremely important to this research platform. Specifically, it was found that γ-oryzanol that occurs in unpolished rice grains elicits a variety of functions in the body, removing the obesity and diabetes by regulating the dopamine pathway [36][37][38][39]. Furthermore, the traditional Japanese soy sauce and rice wine fermentation by-products were found to function as anti-aging agents, and to mitigate longevity-associated lifestyle-related disease [40,41].…”