Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) 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 HbA 1C (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].
|Original language||English (US)|
|Number of pages||9|
|State||Published - Jun 1 2005|
- Insulinotropic compounds
- Magnetic resonance imaging
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism