A Whey Protein Hydrolysate Promotes Insulinotropic Activity in a Clonal Pancreatic β-Cell Line and Enhances Glycemic Function in ob/ob Mice1–3

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.

Nutrient regulation of insulin secretion and action

“…However, negative effects of high concentrations of arginine have been reported and these stem from the effect of enhancing velocity of inducible nitric oxide synthase (iNOS) through substrate stimulation, which may be harmful to the b-cell if cellular antioxidant defences are overwhelmed ). Finally, branched-chain amino acids (BCAAs), consisting of leucine, isoleucine and valine, are also reported to play an influential role in mediating insulin exocytosis , Gaudel et al 2013, while enhanced plasma levels correlated with increased IR in the presence of elevated lipids (Newgard 2012, Lu et al 2013. Interestingly, consumption of dairy products, which are a rich source of BCAAs, has been associated with improvements in both weight loss and T2DM management (Tremblay & Gilbert 2009, Jakubowicz & Froy 2013; consumption of whey protein hydrolysates have been suggested to improve fasting insulin levels, insulin release and glycaemic control in in vivo animal models and in obese and T2DM human subjects (Gaudel et al 2013, Jakubowicz & Froy 2013.…”

“…Finally, branched-chain amino acids (BCAAs), consisting of leucine, isoleucine and valine, are also reported to play an influential role in mediating insulin exocytosis , Gaudel et al 2013, while enhanced plasma levels correlated with increased IR in the presence of elevated lipids (Newgard 2012, Lu et al 2013. Interestingly, consumption of dairy products, which are a rich source of BCAAs, has been associated with improvements in both weight loss and T2DM management (Tremblay & Gilbert 2009, Jakubowicz & Froy 2013; consumption of whey protein hydrolysates have been suggested to improve fasting insulin levels, insulin release and glycaemic control in in vivo animal models and in obese and T2DM human subjects (Gaudel et al 2013, Jakubowicz & Froy 2013. However, the precise mechanism of these positive effects are not fully understood, but are believed to involve increased protein synthesis and possibly thermogenesis via activation of mammalian target of rapamycin (mTOR) signalling, increased anaplerosis and, in the case of leucine, enhanced allosteric activation of GDH that leads to increased TCA activity in the b-cell ( Fig.…”

Insulinotropic Effects of Whey: Mechanisms of Action, Recent Clinical Trials, and Clinical Applications

“…Gaudel et al [20] investigated the effect of WPH on glucose-induced insulin secretion in a pancreatic beta-cell line over 8 weeks in mice. WPH improved blood glucose clearance, decreased hyperinsulinemia and increased beta-cell secretion of insulin in the ob/ob mice.…”

“…These components are thought to be responsible for much of the functional benefits of whey protein on human health [15,18]. The degree and type of hydrolysis impact the effects of whey protein [10,19,20,21,22,23,24,25,26]. Whey protein is rich in the branched chain amino acids (BCAAs) isoleucine, leucine and valine, which along with its bioactive peptides may indirectly affect the glycemic response [6].…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Furthermore, WPH are now referred to as novel antidiabetic agents that affect glycemia in animals and humans. WPH has proven to ameliorate blood glucose clearance, reducing hyperinsulinemia and restoring pancreatic islet capacity to secrete insulin in response to glucose in ob/ob mice [337]. Therefore, besides its well-known effects on cardiovascular and endocrine systems, exercise alone can also influence gut microbiota composition, although the impact of exercise on gut motility and transit time must also be considered in further studies [334].…”