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Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the Akt/eNOS pathway
Author(s) -
Taguchi Kumiko,
Hida Mari,
Hasegawa Mami,
Matsumoto Takayuki,
Kobayashi Tsuneo
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500618
Subject(s) - enos , endothelial dysfunction , protein kinase b , medicine , endocrinology , diabetes mellitus , pi3k/akt/mtor pathway , endothelium , nitric oxide , nitric oxide synthase type iii , endothelial stem cell , streptozotocin , chemistry , phosphorylation , signal transduction , nitric oxide synthase , biochemistry , in vitro
Scope Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications. Polyphenols may represent beneficial dietary components eliciting cardiovascular protection. Although we previously reported that the polyphenol morin (MO) ameliorated diabetes‐induced endothelial dysfunction, the underlying mechanism remains unclear. Here, we investigated protective effects and mechanisms of MO in streptozotocin STZ induced diabetic aorta endothelial dysfunction. Methods and results Diabetes was induced by tail vein injection of STZ (200 mg/kg). At 12 wk after injection, the thoracic aorta was isolated and endothelial function was assessed by acetylcholine (ACh) induced, endothelial‐dependent vasorelaxation in aortas. Nitric oxide (NO) levels and endothelial NO synthase (eNOS), phosphorylated‐eNOS (p‐eNOS), Akt, and phosphorylated‐Akt (p‐Akt) levels were also evaluated in aortas. Diabetic aortas showed attenuated endothelial function, which was improved by MO treatment. MO treatment alone increased NO levels and endothelial‐dependent relaxation responses via Akt signaling, although ACh did not activate this pathway. Moreover, MO upregulated p‐Akt (at Ser473 and Thr308) and p‐eNOS (at Ser1177) expression in diabetic aortas, but ACh stimulation had no effect on p‐Akt and p‐eNOS levels. Conclusion These results indicate a novel role for MO in protection against endothelial dysfunction in diabetes. The protective effects of MO are dependent on Akt‐dependent activation of eNOS signaling.