Sea cucumber intestinal hydrolysates alleviate insulin resistance through regulating IRS1/PI3K/AKT signaling pathway mediated by glutamine metabolism in high-fat and high-sucrose diet-induced mice

It has been reported that sea cucumber intestine hydrolysates (SCIH) could promote glutamine metabolism in mice, while there is a close connection between glutamine metabolism and insulin sensitivity. However, the effect of SCIH on insulin resistance is still unclear. The results showed that SCIH hydrolyzed by flavor protease had significant activity using the insulin-induced HepG2 cell model. Animal experiments exhibited that SCIH supplementation significantly improved the high-fat and high-sucrose diet-induced impaired glucose tolerance, reduced fasting serum glucose and glycosylated serum protein. Besides, SCIH ameliorated islet vacuolization and decreased the pancreas TNF-α and IL-6 by 32.1% and 36.2%, respectively. Immunofluorescence staining results showed that SCIH promoted insulin secretion. Interestingly, SCIH significantly increased the liver glutamine levels and upregulated the expression of glutaminase1 (GLS1) and glutamate dehydrogenase 1 (GLUD1). Furthermore, SCIH increased liver acetyl-CoA levels to enhance histone acetylation and activate the gene transcription and translation on glucose metabolism-related IRS/PI3K/AKT signaling pathway, thereby attenuating insulin resistance. The present findings proposed the potential value for developing functional foods in SCIH utilization.