Common food additive carrageenan inhibits proglucagon expression and GLP-1 secretion by human enteroendocrine L-cells
Sumit Bhattacharyya1,2, Alip Borthakur3, Joanne K Tobacman4,5
1Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Abstract:
Proglucagon mRNA expression and GLP-1 secretion by cultured human L-cells (NCI-H716) were inhibited following exposure to λ-carrageenan, a commonly used additive in processed foods. Carrageenan is composed of sulfated or unsulfated galactose residues linked in alternating alpha-1,3 and beta-1,4 bonds and resembles the endogenous sulfated glycosaminoglycans. However, carrageenan has unusual alpha-1,3-galactosidic bonds, which are not innate to human cells and are implicated in immune responses. Exposure to carrageenan predictably causes inflammation, and carrageenan impairs glucose tolerance and contributes to insulin resistance. When cultured human L-cells were deprived overnight of glucose and serum and then exposed to high glucose, 10% FBS, and λ-carrageenan (1 µg/ml) for 10 minutes, 1 h, and 24 h, mRNA expression of proglucagon and secretion of GLP-1 were significantly reduced, compared to control cells not exposed to carrageenan. mRNA expression of proglucagon by mouse L-cells (STC-1) was also significantly reduced and supports the findings in the human cells. Exposure of co-cultured human intestinal epithelial cells (LS174T) to the spent media of the carrageenan-treated L-cells led to a decline in mRNA expression of GLUT-2 at 24 h. These findings suggest that ingestion of carrageenan-containing processed foods may impair the production of GLP-1, counteract the effect of GLP-1 receptor agonists and induce secondary effects on intestinal epithelial cells.
Insights
λ-carrageenan, a food additive, significantly reduces proglucagon mRNA and GLP-1 secretion in human L-cells. This suggests processed foods containing carrageenan may negatively impact glucose regulation and insulin sensitivity.
Area of Science:
- Endocrinology
- Gastroenterology
- Food Science
Background:
- Carrageenan, a food additive, is structurally similar to glycosaminoglycans but possesses unique alpha-1,3-galactosidic bonds.
- Carrageenan is known to induce inflammation, impair glucose tolerance, and contribute to insulin resistance.
Purpose of the Study:
- To investigate the effect of λ-carrageenan on proglucagon mRNA expression and glucagon-like peptide-1 (GLP-1) secretion in human L-cells.
- To examine the impact of carrageenan on intestinal epithelial cells.
Main Methods:
- Cultured human L-cells (NCI-H716) and mouse L-cells (STC-1) were exposed to λ-carrageenan under high glucose and serum conditions.
- Proglucagon mRNA expression and GLP-1 secretion were measured at various time points (10 minutes, 1 hour, 24 hours).
- Co-cultured human intestinal epithelial cells (LS174T) were exposed to spent media from carrageenan-treated L-cells to assess GLUT-2 mRNA expression.
Main Results:
- λ-carrageenan significantly inhibited proglucagon mRNA expression and GLP-1 secretion in human L-cells.
- Similar inhibition of proglucagon mRNA expression was observed in mouse L-cells.
- Exposure to spent media from carrageenan-treated L-cells reduced GLUT-2 mRNA expression in intestinal epithelial cells.
Conclusions:
- Ingestion of carrageenan-containing processed foods may disrupt GLP-1 production.
- Carrageenan's effects could counteract GLP-1 receptor agonists.
- Carrageenan may induce secondary adverse effects on intestinal epithelial cells, potentially impacting glucose metabolism.
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