Dietary Apostichopus japonicus Alleviates Diabetes Symptoms and Modulates Genes Expression in Kidney Tissues of db/db Mice

摘要

The effects of Apostichopus japonicus enzymatic hydrolysate on the regulation of dyslipidemia, pathoglycemia, and transcription changes in kidney tissues of db/db mice were evaluated. In this study, the symptoms of diabetes in db/db mice were alleviated after 10 weeks of treatments with low (db/db + LD group) and high dose (db/db + HD group) of Apostichopus japonicus enzymatic hydrolysate, and the high dose treatment showed a better antidiabetic effect. Compared with the db/db group, the fasting blood glucose levels (36.84 +/- 7.82 vs 25.18 +/- 6.84 mmol/L, P 0.01), the urine glucose levels (45.44 +/- 3.93 vs 22.66 +/- 5.58 mmol/L, P 0.01), and the serum insulin sensitivity index (-4.65 +/- 0.43 vs -4.74 +/- 0.75, P 0.05) in the db/db + HD group were decreased, whereas the fasting plasma insulin (3.12 +/- 1.08 vs 5.54 +/- 1.82 mu g/L, P 0.01) and the serum insulin resistance index (5.01 +/- 2.02 vs 5.96 +/- 2.49, P 0.05) were increased. Subsequently, the kidney transcription profiles were measured in the db/db group and db/db + HD group via microarray, and the results show that Apostichopus japonicus hydrolysate induced differential expression of 77 genes. Among these genes, the down-regulation of genes ntrK1 and ptpN5 played vital roles, as this effect induced the further down-regulation of neurotrophin tyrosine kinase, protein tyrosine phosphatase, and other transcription factors, which are involved in the classical mitogen-activated protein kinases (MAPK) and p38MAPK signaling pathways. The inhibited MAPK and p38MAPK signaling pathways are involved in glycometabolism and the control of lipid metabolism, and they regulate the occurrence and development of diabetic nephropathy.