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

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 -opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPAR systems in diabetic KKA 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 -conglycinin -subunit is a -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 mice, a type 2 diabetes model animal. Soymorphin-5 inhibited hyperglycemia without an increase in plasma insulin levels in KKA 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) pathway and fatty acid -oxidation. The expressions of the mRNA of PPAR 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 -opioid and anxiolytic-like activities did not decrease blood glucose levels in KKA mice. These results suggest that -opioid peptide soymorphin-5 improves glucose and lipid metabolism via activation of the adiponectin and PPAR system and subsequent increases of -oxidation and energy expenditure in KKA mice.