Oral Administration of Corn Zein Hydrolysate Stimulates GLP-1 and GIP Secretion and Improves Glucose Tolerance in Male Normal Rats and Goto-Kakizaki Rats

• Published in: Endocrinology (Philadelphia) Vol. 154; no. 9; pp. 3089 - 3098
• Main Authors: Higuchi, Noriyuki, Hira, Tohru, Yamada, Nao, Hara, Hiroshi
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Oxford University Press 01.09.2013; Endocrine Society
• Subjects: Animals; Biological and medical sciences; Cell Line; Corn; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diet therapy; Diabetes Mellitus, Type 2 - metabolism; Dietary Supplements; Digestion; Enterocytes - drug effects; Enterocytes - metabolism; Enterocytes - secretion; Fundamental and applied biological sciences. Psychology; Gastric Inhibitory Polypeptide - antagonists & inhibitors; Gastric Inhibitory Polypeptide - blood; Gastric Inhibitory Polypeptide - secretion; GIP protein; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - antagonists & inhibitors; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - secretion; Glucagon-Like Peptide-1 Receptor; Glucose; Glucose tolerance; Glucose Tolerance Test; Hydrolysates; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - antagonists & inhibitors; Hypoglycemic Agents - metabolism; Hypoglycemic Agents - therapeutic use; Male; Males; Medical instruments; Mice; Oral administration; Peptides; Polypeptides; Protein Hydrolysates - administration & dosage; Protein Hydrolysates - antagonists & inhibitors; Protein Hydrolysates - metabolism; Protein Hydrolysates - therapeutic use; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Receptors; Receptors, Gastrointestinal Hormone - antagonists & inhibitors; Receptors, Gastrointestinal Hormone - metabolism; Receptors, Glucagon - antagonists & inhibitors; Receptors, Glucagon - metabolism; Up-Regulation - drug effects; Vertebrates: endocrinology; Zein; Zein - administration & dosage; Zein - antagonists & inhibitors; Zein - metabolism; Zein - therapeutic use; Rat; Secretion; Rodentia; Oral administration; Tolerance; Male; Glucose; Glucagon like peptide 1; Vertebrata; Gastrointestinal hormone; Mammalia; Animal; Gastric inhibitory peptide
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2012-2275

We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.