Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents

Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6. doi: 10.1152/ajpendo.90637.2008. Epub 2008 Sep 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Cell Line
  • Cholecystokinin / genetics
  • Dietary Carbohydrates / administration & dosage
  • Dietary Carbohydrates / metabolism
  • Dietary Carbohydrates / pharmacology*
  • Dipeptidyl Peptidase 4 / blood
  • Eating / drug effects
  • Female
  • Fermentation*
  • Gastric Mucosa / metabolism
  • Gene Expression / drug effects
  • Ghrelin / genetics
  • Glucagon-Like Peptide 1 / blood*
  • Humans
  • Insulin / blood
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide YY / blood*
  • Peptide YY / genetics
  • Proglucagon / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Starch / administration & dosage
  • Starch / metabolism
  • Starch / pharmacology
  • Stomach / drug effects


  • Blood Glucose
  • Dietary Carbohydrates
  • Ghrelin
  • Insulin
  • Peptide YY
  • Proglucagon
  • Glucagon-Like Peptide 1
  • Starch
  • Cholecystokinin
  • Dipeptidyl Peptidase 4