title: Phenolic Compounds from Fermented Berry Beverages Modulated Gene and Protein Expression To Increase Insulin Secretion from Pancreatic β-Cells in Vitro.
abstract: Berries are a rich source of bioactive phenolic compounds that are able to bind and inhibit the enzyme dipeptidyl peptidase-IV (DPP-IV), a current target for type-2 diabetes therapy. The objectives were to determine the role of berry phenolic compounds to modulate incretin-cleaving DPP-IV and its substrate glucagon-like peptide-1 (GLP-1), insulin secretion from pancreatic β-cells, and genes and proteins involved in the insulin secretion pathway using cell culture. Anthocyanins (ANC) from 50% blueberry-50% blackberry (Blu-Bla) and 100% blackberry (Bla) fermented beverages at 50 μM cyanidin-3-glucoside equivalents increased (p < 0.05) glucose-stimulated insulin secretion from pancreatic β-cells (iNS-1E) both when applied directly and following simulated absorption through Caco-2 cells (by 233 and 100 μIU insulin/mL, respectively). ANC 50%Blu-Bla and ANC 100%Bla upregulated the gene for incretin hormone GLP-1 (fold-change 3.0 ± 1.4 and 2.0 ± 0.3, respectively) and genes in the insulin secretory pathway including insulin-like growth factor 1 receptor (iGF1R, 2.3 ± 0.6 and 1.6 ± 0.3, respectively), and increased (p < 0.05) the protein expression of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding proteins (IGFBP-2 and 3), and vascular endothelial growth factor (VEGF) in iNS-1E cells. Taken together, anthocyanins, predominantly delphinidin-3-arabinoside, from fermented berry beverages have the potential to modulate DPP-IV and its substrate GLP-1, to increase insulin secretion, and to upregulate expression of mRNA of insulin-receptor associated genes and proteins in pancreatic β-cells.
authors.affiliation: Division of Nutritional Sciences and ‡Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: Division of Nutritional Sciences and ‡Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Elvira Gonzalez
authors.initials: EG
authors.lastname: de Mejia
mesh_terms: D000872:Anthocyanins; D001628:Beverages; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D005285:Fermentation; D005638:Fruit / Q000737:chemistry; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005960:Glucosides; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D018971:Insulin-Like Growth Factor Binding Protein 2; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D010636:Phenols / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D010636:Phenols; D042461:Vascular Endothelial Growth Factor A; C462279:cyanidin-3-O-beta-glucopyranoside; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; C017185:delphinidin
keywords: DPP-IV; anthocyanin; diabetes; insulin; pancreatic β-cells