The enzyme dipeptidyl peptidase-IV (DPP-IV) is expressed by gut epithelial cells. DPP-IV cleaves X-proline dipeptides from the N-terminus of polypeptide hormones including GLP-1, GIP and PYY. DPP-IV causes a deactivation of the incretin hormones GLP-1 and GIP, whereas conversely, by converting PYY136 to PYY336 it allows specific activation of the Y2 receptors in the arcuate nucleus of the hypothalamus leading to hypophagia. Infused PYY336 has been shown to reduce food intake in healthy and obese humans by 30%. Furthermore, high protein meals have been shown to significantly increase plasma PYY336 levels compared to carbohydrate or fat. The role of DPPIV enzyme expression in intestinal cells or the role of individual amino acids on the up regulation of PYY has not been investigated.
Using the Caco-2 human intestinal epithelial cells we investigated whether the effect of specific macronutrients on PYY and DPPIV gene expression. Cells were stimulated for 24 h with 1.59 mM L-leucine, 2.39 mM L-arginine, L-Leu+L-Arg, non essential amino acids (NEAA)×10 concentration and 20 nM glucose. The expression of DPP-IV and PYY136 genes was determined by SYBR-green real time PCR.
Our results showed no change to the DPP-IV and PYY136 gene expression on stimulation with either L-Leu or L-Arg in isolation. However, addition of both L-Leu+L-Arg in combination resulted in a 1.5-fold induction of DPP-IV (P=0.017) gene and 1.8-fold up-regulation of PYY (P=0.019) gene expression. Glucose treatment also caused a 1.4 up-regulation of DPPIV (P=0.041) and a 3.3 up-regulation of PYY1 (P<0.0001) genes. These data show for the first time that PYY gene is expressed in the human gut epithelial cell line Caco-2 and that the increase in plasma PYY336 may therefore be a result of increased expression of both PYY and DPPIV genes in human intestinal cells.
Declaration of funding: Dr M G Zariwala was awarded the Society for Endocrinology Early Career Grant.