ι-Carrageenan Tetrasaccharide from ι-Carrageenan Inhibits Islet β Cell Apoptosis Via the Upregulation of GLP-1 to Inhibit the Mitochondrial Apoptosis Pathway.

ι-Carrageenan performs diversified biological activities but has low bioavailability. ι-Carrageenan tetrasaccharide (ιCTs), a novel marine oligosaccharide prepared by the marine enzyme Cgi82A, was investigated for its effects on insulin resistance in high-fat and high-sucrose diet mice. Oral administration of ιCTs (ιCTs-L 30.0 mg/kg·bw, ιCTs-H 90.0 mg/kg·bw) decreased fasting blood glucose by 35.1% ± 1.41 (P < 0.01) and 27.4% ± 0.420 (P < 0.05), and enhanced glucose tolerance. Besides, ιCTs-L ameliorated islet vacuolization, decreased the β cell apoptosis by 21.8% ± 0.200 (P < 0.05), and promoted insulin secretion by 5.41% ± 0.0173 (P < 0.01) through pancreatic hematoxylin and eosin (H&E) staining, TUNEL staining, and insulin-glucagon immunostaining analysis. Interestingly, ιCTs-L and ιCTs-H treatment increased the incretin GLP-1 content in serum by 22.1% ± 0.402 (P < 0.01) and 10.7% ± 0.0935 (P < 0.05) respectively, through regulating the bile acid levels, which contributed to the inhibition of β cell apoptosis. Mechanically, ιCTs upregulated the expression of the GLP-1 receptor (GLP-1R) and protein kinase A (PKA) in the GLP-1/cAMP/PKA signaling pathway, and further inhibited the expression of cytochrome C and caspase 3 in the mitochondrial apoptotic pathway. In conclusion, this study suggested that ιCTs alleviated insulin resistance by GLP-1-mediated inhibition of β cell apoptosis and proposed a new strategy for developing potential functional foods that prevent insulin resistance.