A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D 2 receptor signalling in mouse islet

• Published in: British journal of pharmacology Vol. 172; no. 18; pp. 4519 - 4534
• Main Authors: Kozuka, Chisayo, Sunagawa, Sumito, Ueda, Rei, Higa, Moritake, Ohshiro, Yuzuru, Tanaka, Hideaki, Shimizu-Okabe, Chigusa, Takayama, Chitoshi, Matsushita, Masayuki, Tsutsui, Masato, Ishiuchi, Shogo, Nakata, Masanori, Yada, Toshihiko, Miyazaki, Jun-Ichi, Oyadomari, Seiichi, Shimabukuro, Michio, Masuzaki, Hiroaki
• Format: Journal Article
• Language: English
• Published: England 01-09-2015
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.13236

γ-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 D
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 D
receptor signalling.
Glucose metabolism and regulation of molecules involved in D
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 D
receptors and a variety of compounds which alter D
receptor signalling.
In islets, γ-oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D
receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by γ-oryzanol. Experiments with siRNA for D
receptors and D
receptor ligands in vitro suggest that γ-oryzanol suppressed D
receptor signalling and augmented GSIS.
γ-Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of γ-oryzanol on D
receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy.