title: Therapeutic effect of exendin-4, a long-acting analogue of glucagon-like peptide-1 receptor agonist, on nerve regeneration after the crush nerve injury.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. yamagen0610@nifty.com
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Amako
authors.forename: Yoritsuna
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Tsuchihara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nukada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arino
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujita
authors.forename: Maki
authors.initials: M
authors.lastname: Uenoyama
authors.forename: Shoichi
authors.initials: S
authors.lastname: Tachibana
authors.forename: Koichi
authors.initials: K
authors.lastname: Nemoto
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D055724:Electrophysiological Phenomena / Q000187:drug effects; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000819:agonists*; D012584:Sciatic Nerve / Q000187:drug effects* / Q000503:physiopathology* / Q000648:ultrastructure; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide