title: Evaluation of glycated glucagon-like peptide-1(7-36)amide in intestinal tissue of normal and diabetic animal models.
abstract: Glucagon-like peptide-1(7-36)amide (tGLP-1) is an important insulin-releasing hormone of the enteroinsular axis which is secreted by endocrine L-cells of the small intestine following nutrient ingestion. The present study has evaluated tGLP-1 in the intestines of normal and diabetic animal models and estimated the proportion present in glycated form. Total immunoreactive tGLP-1 levels in the intestines of hyperglycaemic hydrocortisone-treated rats, streptozotocin-treated mice and ob/ob mice were similar to age-matched controls. Affinity chromatographic separation of glycated and non-glycated proteins in intestinal extracts followed by radioimmunoassay using a fully cross-reacting anti-serum demonstrated the presence of glycated tGLP-1 within the intestinal extracts of all control animals (approximately 19% of total tGLP-1 content). Chemically induced and spontaneous animal models of diabetes were found to possess significantly greater levels of glycated tGLP-1 than controls, corresponding to between 24--71% of the total content. These observations suggest that glycated tGLP-1 may be of physiological significance given that such N-terminal modification confers resistance to DPP IV inactivation and degradation, extending the very short half-life (<3 min) and bioactivity of the native peptide.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Northern Ireland BT52 1SA, Coleraine, UK. m.mooney@ulst.ac.uk
authors.forename: Mark H
authors.initials: MH
authors.lastname: Mooney
authors.forename: Yasser H A
authors.initials: YH
authors.lastname: Abdel-Wahab
authors.forename: Aine M
authors.initials: AM
authors.lastname: McKillop
authors.forename: Finbarr P M
authors.initials: FP
authors.lastname: O'Harte
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006031:Glycosylation; D006854:Hydrocortisone / Q000008:administration & dosage; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009929:Organ Size; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*; D051381:Rats
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D006854:Hydrocortisone