Deficiency of glucagon gene-derived peptides induces peripheral polyneuropathy in mice

Mikio Motegi, Tatsuhito Himeno, Hiromi Nakai-Shimoda, Rieko Inoue, Norio Ozeki, Yusuke Hayashi, Sachiko Sasajima, Mohammad Sarif Mohiuddin, Emi Asano-Hayami, Makoto Kato, Saeko Asano, Emiri Miura-Yura, Yoshiaki Morishita, Masaki Kondo, Shin Tsunekawa, Yoshiro Kato, Koichi Kato, Keiko Naruse, Yusuke Seino, Yoshitaka HayashiJiro Nakamura, Hideki Kamiya

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg−/−) mice were examined. The gcg−/− mice showed tactile allodynia and thermal hyperalgesia at 12–18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg−/− mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 29-10-2020

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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