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Study · Animal study (in vivo) · mouse · 2023

2 results

Human IAPP is a contributor to painful diabetic peripheral neuropathy.

Albariqi MM, Versteeg S, Brakkee EM, Coert JH, Elenbaas BO, Prado J, Hack CE, Höppener JW, Eijkelkamp N

The Journal of clinical investigation17 Apr 2023Cited by 7 (Europe PMC)

PMID36917177 (opens in a new tab)PMCIDPMC10104883 (opens in a new tab)DOI10.1172/jci156993 (opens in a new tab)PepBankPUB-36917177
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Summary

Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage pancreatic islet β cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth and increased levels of mitochondrial reactive oxygen species. hIAPP-transgenic mice, which have elevated plasma hIAPP levels without hyperglycemia, developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intraepidermal nerve fiber (IENF) density. Similarly, hIAPP Ob/Ob mice, which have hyperglycemia in combination with elevated plasma hIAPP levels, had signs of neuropathy, although more aggravated. In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density. Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects. T2DM patients had reduced IENF density and more hIAPP oligomers in the skin compared with non-T2DM controls. Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Safety outcome

    In wild-type mice, pramlintide did not induce the long-lasting allodynia seen with hIAPP injections.

    In plain wordsIn mice, pramlintide did not cause the lasting pain sensitivity seen after hIAPP injection.

    Peptide
    Pramlintide (Symlin)
    Outcome
    No significant changeAllodynia
    Study

    mousen: not reported in source

    wild-type mice
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    Dose not stated · intraplantar and intravenousAs given in this study (mouse).

    Source sentences

    Summary
    Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects.
    1 context sentence
    Summary · context
    In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density.
  2. 02AnimalAnimal study (in vivo)Safety outcome

    In wild-type mice, pramlintide did not induce the loss of intraepidermal nerve fiber density seen with hIAPP injections.

    In plain wordsIn mice, pramlintide did not cause the loss of skin nerve fibers seen after hIAPP injection.

    Peptide
    Pramlintide (Symlin)
    Outcome
    No significant changeIntraepidermal nerve fiber density
    Study

    mousen: not reported in source

    wild-type mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraplantar and intravenousAs given in this study (mouse).

    Source sentences

    Summary
    Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects.
    1 context sentence
    Summary · context
    In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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