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In vivo biological activity of exendin (1–30)

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Abstract

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/Leprdb (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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Authors and Affiliations

  1. Diabetes Section, Diabetes Section National Institute on Aging, National Institutes of Health, USA

    Máire E. Doyle PhD, Michael J. Theodorakis, Michel Bernier & Josephine M. Egan

  2. NMR Unit, Diabetes Section National Institute on Aging, National Institutes of Health, USA

    Patrick McConville & Richard G. S. Spencer

  3. Drug Design and Development Section, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, 21224, Baltimore, MD

    Harold W. Holloway & Nigel H. Greig

  4. Pathology Services Inc., 640 Memorial Drive, 02139, Cambridge, MA

    Margaret M. Goetschkes

Authors
  1. Máire E. Doyle PhD
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  2. Patrick McConville
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  3. Michael J. Theodorakis
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  4. Margaret M. Goetschkes
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  5. Michel Bernier
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  6. Richard G. S. Spencer
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  7. Harold W. Holloway
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  8. Nigel H. Greig
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  9. Josephine M. Egan
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Correspondence to Máire E. Doyle PhD.

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Doyle, M.E., McConville, P., Theodorakis, M.J. et al. In vivo biological activity of exendin (1–30). Endocr 27, 1–9 (2005). https://doi.org/10.1385/ENDO:27:1:001

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