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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].

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Adipose Tissue, Amino Acid Sequence, Animals, Blood Glucose, Body Composition, Bromodeoxyuridine, Cell Proliferation, Diabetes Mellitus, Eating, Exenatide, Glycated Hemoglobin A, Immunoenzyme Techniques, Injections, Intraperitoneal, Insulin, Islets of Langerhans, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Microscopy, Confocal, Molecular Sequence Data, Peptides, Rats, Rats, Inbred F344, Venoms, Weight Gain