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BioMed Research International
Volume 2013, Article ID 315848, 7 pages
Research Article

Therapeutic Effect of Exendin-4, a Long-Acting Analogue of Glucagon-Like Peptide-1 Receptor Agonist, on Nerve Regeneration after the Crush Nerve Injury

1Department of Orthopedic Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
2Division of Environmental Medicine, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
3Orthopedic Surgery, Japan Self Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya-ku, Tokyo 154-0001, Japan
4Department of Medicine, University of Otago Medical School, P.O. Box 913, Dunedin 9054, New Zealand
5The Nukada Institute for Medical and Biological Research, 5-18 Inage-cho, Inage-ku, Chiba 263-0035, Japan

Received 26 April 2013; Revised 11 July 2013; Accepted 14 July 2013

Academic Editor: Levent Sarıkcıoğlu

Copyright © 2013 Koji Yamamoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.