Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are anti-diabetes/obesity hormones secreted from the gut after meal ingestion. We have shown that dietary-resistant starch (RS) increased GLP-1 and PYY secretion, but the mechanism remains unknown. RS is a fermentable fiber that lowers the glycemic index of the diet and liberates short-chain fatty acids (SCFAs) through fermentation in the gut. This study investigates the two possible mechanisms by which RS stimulates GLP-1 and PYY secretion: the effect of a meal or glycemic index, and the effect of fermentation. Because GLP-1 and PYY secretions are stimulated by nutrient availability in the gut, the timing of blood sample collections could influence the outcome when two diets with different glycemic indexes are compared. Thus we examined GLP-1 and PYY plasma levels at various time points over a 24-h period in RS-fed rats. In addition, we tested proglucagon (a precursor to GLP-1) and PYY gene expression patterns in specific areas of the gut of RS-fed rats and in an enteroendocrine cell line following exposure to SCFAs in vitro. Our findings are as follows. 1) RS stimulates GLP-1 and PYY secretion in a substantial day-long manner, independent of meal effect or changes in dietary glycemia. 2) Fermentation and the liberation of SCFAs in the lower gut are associated with increased proglucagon and PYY gene expression. 3) Glucose tolerance, an indicator of increased active forms of GLP-1 and PYY, was improved in RS-fed diabetic mice. We conclude that fermentation of RS is most likely the primary mechanism for increased endogenous secretions of total GLP-1 and PYY in rodents. Thus any factor that affects fermentation should be considered when dietary fermentable fiber is used to stimulate GLP-1 and PYY secretion.

. Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat. Obesity. 2006;14:1523-1534. Objective: To assess the effects of energy dilution with non-fermentable and fermentable fibers on abdominal fat and gut peptide YY (PYY) and glucagon-like peptide (GLP)-1 expressions, three rat studies were conducted to: determine the effects of energy dilution with a non-fermentable fiber, compare similar fiber levels of fermentable and non-fermentable fibers, and compare similar metabolizable energy dilutions with fermentable and non-fermentable fibers. Research Methods and Procedures:In Study 1, rats were fed one of three diets with different metabolizable energy densities. In Study 2, rats were fed diets with similar fiber levels using high amylose-resistant cornstarch (RS) or methylcellulose. In Study 3, rats were fed diets with a similar dilution of metabolizable energy using cellulose or RS. Measurements included food intake, body weight, abdominal fat, plasma PYY and GLP-1, gastrointestinal tract weights, and gene transcription of PYY and proglucagon. Results: Energy dilution resulted in decreased abdominal fat in all studies. In Study 2, rats fed fermentable RS had increased cecal weights and plasma PYY and GLP-1, and increased gene transcription of PYY and proglucagon. In Study 3, RS-fed rats had increased short-chain fatty acids in cecal contents, plasma PYY (GLP-1 not measured), and gene transcription for PYY and proglucagon. Discussion: Inclusion of RS in the diet may affect energy balance through its effect as a fiber or a stimulator of PYY and GLP-1 expression. Increasing gut hormone signaling with a bioactive functional food such as RS may be an effective natural approach to the treatment of obesity.

YY and proglucagon mRNA expression patterns and regulation in the gut. Obesity. 2006;14:683-689. Objective: Peptide YY (PYY) and glucagon-like peptide-1 are important in the control of energy homeostasis and are both secreted from the gut in response to ingested nutrients. However, more studies are needed on nutrient regulation of their gene expression patterns in specific areas of the gut. This study detailed PYY and proglucagon (the gene that encodes glucagon-like peptide-1) gene expression patterns and regulation in the gut. We further examined the regulation of PYY and proglucagon mRNA by a diet containing fermentation-resistant starch (in vivo) and butyrate (in vitro). Research Methods and Procedures: Quantitative real time reverse transcriptase-polymerase chain reaction was used to measure PYY and proglucagon gene expression in epithelial cells collected from the duodenum, jejunum, cecum, and colon in normal Sprague-Dawley rats and in rats fed a resistant starch diet for 4 weeks. The same measurements were also performed in primary epithelial cells collected from the cecum and colon of normal rats after the cells were incubated with butyrate for 3 hours. Results: The gene expression patterns for PYY and proglucagon are similar to their peptide distribution patterns in the gut. Also, PYY and proglucagon mRNA expression were up-regulated in the cecum and colon in resistant-starch-fed rats. Butyrate increased PYY and proglucagon gene expression in a dose-dependent manner in vitro. Discussion: Our data provide evidence that the distal part of the gut has the ability to sense nutrients such as butyrate, resulting in the up-regulation of PYY and proglucagon gene expression.

Scope Dietary prebiotics show potential in anti-diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon-like peptide-1 (GLP-1) consistently released, a potent anti-diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary-resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP-1 is the secondary mechanism. Methods and results In this study, GK rats were fed an RS diet with 30% RS and an energy control diet. After 10 wk, these rats were mated and went through pregnancy and lactation. At the end of the study, pancreatic β cell mass, insulin sensitivity, pancreatic insulin content, total GLP-1 levels, cecal short-chain fatty acid concentrations and butyrate producing bacteria in cecal contents were greatly improved by RS feeding. The offspring of RS-fed dams showed improved fasting glucose levels and normal growth curves. Conclusion Dietary RS is potentially of great therapeutic importance in the treatment of diabetes and improvement in outcomes of pregnancy complicated by diabetes.