Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 1, Pages 212-222Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c06456
Keywords
insulin resistance; iota-carrageenan tetrasaccharide; beta cell apoptosis; GLP-1; bile acids
Funding
- National Key R&D Program of China [2018YFC0311203]
- Fundamental Research Funds for the Central Universities (Ocean University of China) [201861034]
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Research suggests that iota CTs can alleviate insulin resistance caused by a high-fat and high-sucrose diet through multiple pathways, including reducing blood glucose levels, enhancing glucose tolerance, decreasing beta cell apoptosis, and promoting insulin secretion. Additionally, iota CTs increase GLP-1 levels by regulating bile acid levels, which contributes to the inhibition of beta cell apoptosis.
iota-Carrageenan performs diversified biological activities but has low bioavailability. iota-Carrageenan tetrasaccharide (iota CTs), 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 iota CTs (iota CTs-L 30.0 mg/kg.bw, lCTs-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, iota CTs-L ameliorated islet vacuolization, decreased the beta 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, iota CTs-L and iota CTs-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 beta cell apoptosis. Mechanically, iota CTs 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 iota CTs alleviated insulin resistance by GLP-1-mediated inhibition of beta cell apoptosis and proposed a new strategy for developing potential functional foods that prevent insulin resistance.
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