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Impaired Nociception in the Diabetic Ins2+/Akita Mouse

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article numberdb171306
Issue number8
Early online date6 Jun 2018
Accepted/In press18 May 2018
E-pub ahead of print6 Jun 2018
Published1 Aug 2018


  • Impaired nociception in the_VASTANI_Accepted18May2018_GREEN AAM

    Impaired_nociception_in_the_VASTANI_Accepted18May2018_GREEN_AAM.pdf, 1.6 MB, application/pdf

    Uploaded date:20 Jun 2018

    Version:Accepted author manuscript

    © 2018 by the American Diabetes Association.
    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at

King's Authors


The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2+/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical and thermal nociception and a significant loss of intraepidermal nerve fibers. Electrophysiological investigations of skin-nerve preparations identified a reduced rate of action potential discharge in Ins2+/Akita mechanonociceptors compared to wildtype littermates, whereas the function of low threshold A-fibers was essentially intact. Studies of isolated sensory neurons demonstrated a markedly reduced heat responsiveness in Ins2+/Akita DRG neurons, but a mostly unchanged function of cold sensitive neurons. Restoration of normal glucose control by islet transplantation produced a rapid recovery of nociception, which occurred before normoglycemia had been achieved. Islet transplantation also restored Ins2+/Akita intraepidermal nerve fiber density to the same level as wildtype mice, indicating that restored insulin production can reverse both sensory and anatomical abnormalities of diabetic neuropathy in mice. The reduced rate of action potential discharge in nociceptive fibers and the impaired heat responsiveness of Ins2+/Akita DRG neurons suggests that ionic sensory transduction and transmission mechanisms are modified by diabetes.

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