Exposure to low concentration of the common food additive carrageenan (CGN) leads to impaired glucose tolerance and insulin resistance in C57BL/6J mice, due to CGN’s pro-inflammatory effects and changes in phospho-IRS1 phosphorylation. CGN is a sulfated polysaccharide with α-1,3 and β-1,4 galactosidic bonds. Other studies showed: 1) CGN reduced activity of arylsulfatase B, which removes sulfate groups from N-acetylgalactosamine 4-sulfate residues of chondroitin 4-sulfate (C4S) and dermatan sulfate; and 2) galectin-3 binds less with C4S when ARSB is reduced. Increase in galectin-3, which binds to β-galactosides, was reported to inhibit insulin signaling (Li P et al) by effects on the insulin receptor. This background led to the current assessment of effects of the no-CGN diet on galectin-3 levels in serum and galectin-3 mRNA in circulating mononuclear cells. Blood samples were obtained from adults with prediabetes before and after dietary intervention. Baseline serum galectin-3 values averaged 8.94 ng/ml (range 4.06-12.64). In 7 patients on a no-CGN diet for 12 weeks, the mean level declined to 7.25 ng/ml (p=0.006, paired t-test). In contrast, serum galectin-3 was unchanged in participants on the CGN-containing control diet and increased by over 2 ng/ml in subjects on their regular diet. mRNA expression of galectin-3 (NGALS3) in circulating mononuclear cells of patients on the no-CGN diet declined by 69%, and increased by 36% in the CGN-containing diet group and by 98% in the regular diet group (p=0.0002, 1-way ANOVA). Also, serum galectin-3 levels increased to 1.72 times baseline in C57BL/6J mice given CGN in their water supply for 12 weeks. In HepG2 cells, exogenous galectin-3 (25 µg/ml) inhibited insulin-induced glucose uptake by 39%, and was highly correlated with decline in tyrosine phosphorylation of IRS-1. These findings suggest that CGN contributes to glucose intolerance and insulin resistance, in part, by effects on galectin-3.


J.K. Tobacman: None. S. Bhattacharyya: None. L. Feferman: None.

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