Soymorphin-5, a soy-derived mu-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPAR alpha systems in diabetic KKA(y) mice

作者：Yamada Yuko; Muraki Aya; Oie Mariko; Kanegawa Norimasa; Oda Ayako; Sawashi Yurina; Kaneko Kentaro; Yoshikawa Masaaki; Goto Tsuyoshi; Takahashi Nobuyuki; Kawada Teruo; Ohinata Kousaku^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2012, 302(4): E433-E440.

DOI：10.1152/ajpendo.00161.2011

• type 2 diabetes
• insulin resistance
• blood glucose
• adiponectin
• peroxisome proliferator-activated receptor-alpha

Yamada Y, Muraki A, Oie M, Kanegawa N, Oda A, Sawashi Y, Kaneko K, Yoshikawa M, Goto T, Takahashi N, Kawada T, Ohinata K. Soymorphin-5, a soy-derived mu-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPAR alpha systems in diabetic KKA(y) mice. Am J Physiol Endocrinol Metab 302: E433-E440, 2012. First published November 29, 2011; doi:10.1152/ajpendo.00161.2011.-Soymorphin-5 (YPFVV) derived from soybean beta-conglycinin beta-subunit is a mu-opioid agonist peptide having anxiolytic-like activity. Here, we show that soymorphin-5 improves glucose and lipid metabolism after long-term oral administration to KKA(y) mice, a type 2 diabetes model animal. Soymorphin-5 inhibited hyperglycemia without an increase in plasma insulin levels in KKA(y) mice. Soymorphin-5 also decreased plasma and liver triglyceride (TG) levels and liver weight, suggesting that soymorphin-5 improved lipid metabolism. Soymorphin-5 increased plasma adiponectin concentration and liver mRNA expression of AdipoR2, a subtype of adiponectin receptor that is involved in stimulating the peroxisome proliferator-activated receptor (PPAR)alpha pathway and fatty acid beta-oxidation. The expressions of the mRNA of PPAR alpha and its target genes acyl-CoA oxidase, carnitine palmitoyltransferase 1 A, and uncoupling protein-2, in the liver were also increased after oral administration of soymorphin-5. Furthermore, des-Tyr-soymorphin-5 (PFVV) without mu-opioid and anxiolytic-like activities did not decrease blood glucose levels in KKA(y) mice. These results suggest that mu-opioid peptide soymorphin-5 improves glucose and lipid metabolism via activation of the adiponectin and PPAR alpha system and subsequent increases of beta-oxidation and energy expenditure in KKA(y) mice.

• 出版日期2012-2