Beneficial Effects of Exendin-4 on Experimental Polyneuropathy in Diabetic Mice

• DOI: 10.2337/db10-1462
• Publication Date: 2011-08-02T04:22:29Z
• Authors: Tatsuhito Himeno; Hideki Kamiya; Keiko Naruse; Norio Harada; Nobuaki Ozaki; Yusuke Seino; Taiga Shibata; Masaki Kondo; Jiro Kato; Tetsuji Okawa; Ayako Fukami; Yoji Hamada; Nobuya Inagaki; Yutaka Seino; Daniel J. Drucker; Yutaka Oiso; Jiro Nakamura
• Keywords: Dorsal root ganglion; Neurite; Hypoalgesia; Diabetic Neuropathy

OBJECTIVE The therapeutic potential of exendin-4, an agonist the glucagon-like peptide-1 receptor (GLP-1R), on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced mice was investigated. RESEARCH DESIGN AND METHODS presence GLP-1R lumbar dorsal root ganglion (DRG) evaluated by immunohistochemical analyses. DRG neurons were dissected from C57BL6/J and cultured with or without Schwann cell–conditioned media absence GLP-1 (7–37) exendin-4. Then neurite outgrowth determined. In animal-model experiments, made STZ administration, after 12 weeks diabetes, exendin-4 (10 nmol/kg) intraperitoneally administered once daily for 4 weeks. Peripheral nerve function determined current perception threshold motor sensory conduction velocity (MNCV SNCV, respectively). Sciatic blood flow (SNBF) intraepidermal fiber densities (IENFDs) also evaluated. RESULTS expression confirmed. significantly promoted neurons. Both agonists accelerated impaired that mimicked condition. At doses used, had no effect glucose HbA1c levels. Hypoalgesia delayed MNCV SNCV improved affecting reduced SNBF. decreased IENFDs sole skins ameliorated CONCLUSIONS Our findings indicate ameliorates severity DPN, which may be achieved its direct actions their axons.