Trefoil factor 3 (TFF3) expression is regulated by insulin and glucose

Abstract

Introduction: Trefoil factors are effector molecules in gastrointestinal tract physiology. They are classified into three groups: the gastric peptides (TFF1), spasmolytic peptide (TFF2) and intestinal trefoil factor (TFF3). Previous studies have shown that trefoil factors are located and expressed in human endocrine pancreas suggesting that TFF3 play a role in: a) pancreatic cells migration, b) β-cell mitosis, and c) pancreatic cells regeneration. We speculated that the presence of TFF3 in pancreas, could be associated to a possible regulation mechanism by insulin and glucose. To date, there are not reports whether the unbalance in carbohydrate metabolism observed in diabetes could affect the production or expression of TFF3.Methods: We determined the TFF3 levels and expression by immunoassay (ELISA) and semi-quantitative RT-PCR technique respectively, of intestinal epithelial cells (HT-29) treated with glucose and insulin. Also,Real Time-PCR (RTq-PCR) was done.Results: Increasing concentrations of glucose improved TFF3 expression and these levels were further elevated after insulin treatment. Insulin treatment also led to the up-regulation of human sodium/glucose transporter 1 (hSGLT1), which further increases intracellular glucose levels. Finally, we investigated theTFF3 levels in serum of diabetes mellitus type 1 (T1DM) and healthy patients. Here we shown that serum TFF3 levels were down-regulated in T1DM and this levels were up-regulated after insulin treatment. Also, the TFF3 levels of healthy donors were up-regulated 2 h after breakfast.Conclusion: Our fi ndings suggest for the fi rst time that insulin signaling is important for TFF3 optimal expression in serum and intestinal epithelial cells.