title: In vivo biological activity of exendin (1-30).
abstract: Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Lepr(db)/Lepr(db) (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA1C (control 9.5 +/- 0.2% vs treated 7.9 +/- 0.2%, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 +/- 1.8% exendin (1-30) vs 6.5 +/- 0.5% control].
authors.affiliation: Diabetes Section National Institute on Aging, National Institutes of Health. Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore MD 21224, USA. medoyle@dental.ufl.edu
authors.forename: Máire E
authors.initials: ME
authors.lastname: Doyle
authors.forename: Patrick
authors.initials: P
authors.lastname: McConville
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Theodorakis
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Goetschkes
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.forename: Richard G S
authors.initials: RG
authors.lastname: Spencer
authors.forename: Harold W
authors.initials: HW
authors.lastname: Holloway
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics; D004435:Eating / Q000187:drug effects; D000077270:Exenatide; D006442:Glycated Hemoglobin / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010455:Peptides / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D014688:Venoms; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D001973:Bromodeoxyuridine; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007328:Insulin; D010455:Peptides; D014688:Venoms