Proceedings of The Physiological Society
AstraZeneca (2010) Proc Physiol Soc 18, C12 and PC12
Ileal administration of zein hydrolysate stimulates glucagon-like peptide-1 secretion and attenuates hyperglycaemia induced by intraperitoneal glucose administration in rats
T. Hira1, T. Mochida1, H. Hara1
1. Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Glucagon-like peptide-1 (GLP-1) is one of the incretin hormones that enhance insulin secretion from pancreatic beta cells. GLP-1 is secreted from enteroendocrine L cells mainly located in the distal small intestine, in response to nutrient ingestion. We recently demonstrated that a protein hydrolysate prepared from corn zein (ZeinH) strongly stimulates GLP-1 secretion from rat small intestine under anaesthesia (Hira et al. 2009). In this study, we examined whether ZeinH administered into the ileum induces GLP-1 secretion and affects glycaemia in conscious rats during a glucose tolerance test. Silicone catheters (1 mm diameter) were inserted into the jugular vein and the ileum of male Sprague-Dawley rats (250-300 g) under anaesthesia with sodium pentobarbital (40 mg/kg i.p.). After 2-3 days recovery an intraperitoneal glucose tolerance test was performed in conscious rats. Water (2 ml), ZeinH solution (500 mg in 2 ml) or meat hydrolysate (MHY) solution (500 mg in 2 ml) were administered into the ileum through the catheter at -30 min. Glucose (1 g/2 ml/kg body weight) was injected intraperitoneally 30 min after the ileal administration of test liquids. Blood samples were collected from the jugular catheter before the ileal administration (-30 min) and 0, 15, 30 and 60 min after glucose injection. Glucose, insulin, total GLP-1 and active GLP-1 were measured in plasma. Peak plasma glucose levels in ZeinH-treated rats (178.7 ± 15.7 at 15 min, n=6, means ± S.E.M.) were significantly lower (P<0.05, Fisher’s PLSD test) than those in water-treated rats (266.9 ± 33.7 at 15 min, n=7). Glucose levels in MHY-treated rats (n=6) were not significantly lower than those in water-treated rats. Insulin secretion was enhanced by ileal administration of ZeinH, but not by MHY. From these results, it was predicted that GLP-1 secretion would be induced by ileal ZeinH but not by ileal MHY. However, total GLP-1 levels were increased by both treatments. In addition, GLP-1 increments at 0 min (+0.64 ± 0.13 in ZeinH group and 0.40 ± 0.01 nM in MHY group) and 30 min (+0.62 ± 0.20 in ZeinH group and 0.49 ± 0.07 nM in MHY group) were significantly higher (P<0.05, Fisher’s PLSD test) than those in water-treated rats (-0.10 ± 0.17 nM at 0 min and 0.03 ±0.24 nM at 30 min). In contrast to total GLP-1, active GLP-1 levels were significantly increased (P<0.05, Fisher’s PLSD test) only in ZeinH-treated rats (from 6.02 ± 2.62 pM at -30 min to 17.32 ± 3.50 pM at 0 min). These results demonstrate that ileal administration of a protein hydrolysate, ZeinH induces GLP-1 secretion and attenuates hyperglycaemia, and suggest that the activity of secreted GLP-1 is retained following ZeinH but not after MHY administration.
Where applicable, experiments conform with Society ethical requirements