title: A whey protein hydrolysate promotes insulinotropic activity in a clonal pancreatic β-cell line and enhances glycemic function in ob/ob mice.
abstract: Whey protein hydrolysates (WPHs) represent novel antidiabetic agents that affect glycemia in animals and humans, but little is known about their insulinotropic effects. The effects of a WPH were analyzed in vitro on acute glucose-induced insulin secretion in pancreatic BRIN-BD11 β cells. WPH permeability across Caco-2 cell monolayers was determined in a 2-tiered intestinal model. WPH effects on insulin resistance were studied in vivo following an 8-wk oral ingestion (100 mg/kg body weight) by ob/ob (OB-WPH) and wild-type mice (WT-WPH) compared with vehicle control (OB and WT groups) using a 2 × 2 factorial design, genotype × treatment. BRIN-BD11 cells showed a robust and reproducible dose-dependent insulinotropic effect of WPH (from 0.01 to 5.00 g/L). WPH bioactive constituents were permeable across Caco-2 cell monolayers. In the OB-WPH and WT-WPH groups, WPH administration improved glucose clearance after a glucose challenge (2 g/kg body weight), as indicated by differences in the area under curves (AUCs) (P ≤ 0.05). The basal plasma glucose concentration was not affected by WPH treatment in either genotype. The plasma insulin concentration was lower in the OB-WPH than in the OB group (P ≤ 0.005) but was similar between the WT and WT-WPH groups; the interaction genotype × treatment was significant (P ≤ 0.005). Insulin release from pancreatic islets isolated from the OB-WPH group was greater (P ≤ 0.005) than that from the OB group but did not differ between the WT-WPH and WT groups; the interaction genotype × treatment was not significant. In conclusion, an 8-wk oral administration of WPH improved blood glucose clearance, reduced hyperinsulinemia, and restored the pancreatic islet capacity to secrete insulin in response to glucose in ob/ob mice. Hence, it may be useful in diabetes management.
authors: School of Biomolecular and Biomedical Sciences, Health Sciences Centre, University College Dublin, Belfield, Dublin, Ireland.
authors: Celine
authors: C
authors: Gaudel
authors: Alice B
authors: AB
authors: Nongonierma
authors: Samuel
authors: S
authors: Maher
authors: Sarah
authors: S
authors: Flynn
authors: Mauricio
authors: M
authors: Krause
authors: Brian A
authors: BA
authors: Murray
authors: Phillip M
authors: PM
authors: Kelly
authors: Alan W
authors: AW
authors: Baird
authors: Richard J
authors: RJ
authors: FitzGerald
authors: Philip
authors: P
authors: Newsholme
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D008894:Milk Proteins / Q000494:pharmacology*; D011492:Protein Hydrolysates / Q000494:pharmacology*; D000067816:Whey Proteins
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008894:Milk Proteins; D011492:Protein Hydrolysates; D000067816:Whey Proteins