Beta-glucan-rich Barley improves glucose tolerance via increased GLP-1 secretion


【Introduction】
In an animal study, the authors have confirmed that barley consumption stimulates the production of short-chain fatty acids (SCFAs) by intestinal bacteria *1, but did not measure gastrointestinal hormone secretion in this study. Previous studies have shown that barley intake increases GLP-1 secretion and improves insulin resistance through changes in the intestinal microbiome and an increase in SCFAs levels *2. On the other hand, there is a report that barley β-glucan intake stimulated fermentation in the cecum but did not affect glucose tolerance or insulin secretion*3.
Therefore, the main objective of this study was to clarify whether the mechanism of improving glucose tolerance is due to the effect of β-glucan-rich barley (high β-glucan barley) on increasing GLP-1 secretion.

【Materials and Methods】
Five-week-old male C57BL/6J mice were acclimated for one week. The mice were fed a high-fat diet (50% lipid energy ratio) with the addition of powder of Kirarimochi, a variety of HGB, and a cellulose-containing diet (C). Eight mice in each group were kept for 83 days. The total dietary fiber content was adjusted to be 5% in both groups.

Bodyweight and feed intake were measured three times a week, and an oral glucose tolerance test (OGTT) was performed in the last week. At the end of the study period, the animals were dissected and subjected to biochemical tests, measurement of the liver, cecum, and adipose tissue weight, and analysis of mRNA expression and L-cell count by real-time PCR in the ileum. A series of tests were performed twice, the first time to evaluate the GLP-1 concentration in the portal vein and cecum, and the second time to evaluate the amount of SCFAs in the cecal contents; in the second time, growth records, organ weights, and OGTT were also performed.

【Results】
There were no significant differences in weight gain, food intake, or food efficiency ratio between the two groups. There were no significant differences in liver weight and adipose tissue (retroperitoneal, epididymal, mesenteric fat) between the two groups. However, the weight of cecum with digesta was significantly higher in HGB group than in C group. Similar results were obtained for the second experiment.

Serum concentrations of total cholesterol, triglycerides, free fatty acids, glucose, insulin, and leptin were not significantly different between the two groups.

In the OGTT at the first experiment, the blood glucose levels at 15- and 60-minute after glucose intake were significantly lower in HGB group than in C group. The -30 and 60-minute values in the second experiment were significantly lower in HGB group than in C group. The area under the blood glucose elevation curve (AUC) was significantly lower in HGB group than in C group for both the first and second experiments.

The cecal pool size of SCFAs, acetic acid, and propionic acid in the were significantly higher in HGB group than in C group. GLP-1 levels in the portal vein and cecum were significantly higher in HGB group compared with C group.

The experimentally determined mRNA levels in ileum, neuro D was elevated in HGB group than in C group. The expression levels of proglucagon (PGCG), prohormone convertase 1/3 (PC1/3), peroxisome proliferator-activated receptor β/δ (PPARβ/δ), G-protein-coupled bile acid receptor 1 (GPBAR1), G-protein-coupled receptor 43 (GPR43), and neurogenin 3 (NGN3) were not significantly different.

The number of L cells in the ileum was significantly higher in HGB group than in C group.

【Discussion and Conclusion】
The improvement of glucose tolerance in mice on a high-fat diet containing HGB group was suggested due to increased GLP-1 secretion.

The mRNA expression levels of PGCG, a precursor of GLP-1, PC1/3, which converts PGCG to GLP-1, and PPARβ/δ, which is involved in GLP-1 secretion in the ileum, were not significantly different between C group and HGB group, but neuro D, which reflects the number of L cells, was significantly higher in HGB group compared with C group.

This study confirmed for the first time an increase in L-cell number in the ileum that causes an increase in GLP-1 secretion without altering the expression of mRNAs associated with GLP-1 secretion. Considering the results of the authors' previous study*1, the increase in number of L cells and the subsequent increase in GLP-1 levels may have been induced by producing SCFAs.

【Research institution】
Otsuma Women's University,

*1 Nutrients 12, 11, 3546, 2020
*2 PLoS One 13, e0196579, 2018
*3 Nutr Res 35, 2, 162-8, 2015


High β-Glucan Barley Supplementation Improves Glucose Tolerance by Increasing GLP-1 Secretion in Diet-Induced Obesity Mice
Nutrients 13, 2, 527, 2021