Dose-Effect of a 6-week treatment with PEP2DIA® on sucrose tolerance in Goto-Kakizaki (GK) rats
The study was designed to evaluate the dose-effect of PEP2DIA, a patented milk protein hydrolysate on glycemic control of type 2 diabetic Goto-Kakizaki (GK) rats treated for 6 weeks from weaning. The 6 week-treatment with PEP2DIA (63mg/kg, 88.6mg/kg and 126mg/kg) did not decrease fasting plasma glucose of GK rats, but improved sucrose tolerance with the best effect at the dose of 63mg/kg. Insulin response to sucrose was lower than control after PEP2DIA treatment at all the doses tested with the strongest decrease with 63mg/kg of PEP2DIA. 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 (63mg/kg), FAS and SREBP-1c gene expressions were significantly decreased in retroperitoneal adipose tissue of GK rats, suggesting that PEP2DIA inhibited lipogenesis. PEP2DIA treatment induced strong increases in GLP-1 plasma level at all the doses tested but the difference reached significance only with 63 and 126mg/kg of PEP2DIA. This effect was not the consequence of an inhibition of DPP-4. An inhibition of alpha-glucosidase in duodenum but not in jejunum was observed after the 6-weektreatment with PEP2DIA, maybe due to a too short time after compound administration for organ sampling. Moreover, in retroperitoneal adipose tissue but not in liver, PEP2DIA at the lowest dose tested (63mg/kg), significantly decreased gene expression of both SREBP-1c and FAS, suggesting a beneficial effect on triglyceride accumulation in adipose tissue.