Dose-Effect of a 6-week treatment with PEP2DIA®, a Patented Milk Protein Hydrolysate on Sucrose Tolerance in Goto-Kakizaki (GK) Rats

Abstract

Objectives The study was designed to evaluate the dose-effect of PEP2DIA(r)(PEP), a milk protein hydrolysate on glycemic control of type 2 diabetic Goto-Kakizaki (GK) rats treated for 6 weeks. Methods Rats (n = 10) were treated with PEP solubilized in spring water by oral gavage once a day for 6 weeks. The effects of a 6-week-administration of PEP (63 mg/kg, 88.6 mg/kg and 126 mg/kg per os) were evaluated on sucrose tolerance and insulin response to sucrose in type 2 diabetic GK rats from weaning (3 weeks) to adult age (9 weeks). Circulating GLP-1 concentration and DDP-4 activity, α-glucosidase activity in duodenum and jejunum, Fatty Acid Synthase (FAS) and Sterol regulatory element-binding protein 1 (SREBP-1c) gene expressions in liver and retroperitoneal adipose tissue were also measured. PEP is a patented milk protein hydrolysate containing AP dipeptides which inhibit alpha glucosidase. The alpha-glucosidase inhibitor Acarbose (40 mg/kg) was used as reference. Results The 6 week-treatment with PEP at 3 doses improved sucrose tolerance with the best effect at the dose of 63 mg/kg. Insulin response to sucrose was lower than control after PEP treatment at all the doses tested with the strongest decrease with 63 mg/kg of PEP. This decrease in insulin response seems to be at least in part the consequence of an improvement of the insulin resistance of the GK rats. At the lowest dose tested (63 mg/kg), FAS and SREBP-1c gene expressions were significantly decreased in retroperitoneal adipose tissue of GK rats, suggesting that PEP inhibited lipogenesis. PEP treatment induced strong increases in GLP-1 plasma level at all the doses tested but the difference reached significance only with 63 and 126 mg/kg of PEP. An inhibition of alpha-glucosidase in duodenum but not in jejunum was observed after the 6-week-treatment with PEP. Moreover, in retroperitoneal adipose tissue, PEP at the lowest dose tested (63 mg/kg), significantly decreased gene expression of both SREBP-1c and FAS, suggesting a beneficial effect on triglyceride accumulation in adipose tissue Conclusions These results showed that PEP2DIA(r) could have a beneficial effect on glycemic control of type 2 diabetic GK rats and suggest that this milk protein hydrolysate should be beneficial Impaired Fasting Glucose or Impaired Glucose Tolerance subjects for delaying the progression to overt type 2 diabetes. Funding Sources INGREDIA S.A.

A comprehensive review on the glucoregulatory properties of food-derived bioactive peptides

“…Table 1 summarizes recent food-derived bioactive peptides with α-glucosidase and α-amylase inhibitory activities. Six weeks treatment of type 2 diabetic Goto-Kakizaki rats with PEP2DIA, a milk protein hydrolysate containing dipeptides with α-glucosidase inhibitory effect, has been reported to improve glycemic control in these rats ( Boulier, Auger, & Romelard, 2021 ). Plant proteins are another source to produce α-glucosidase inhibitory peptides.…”