RGD Reference Report - Systemic Insulin-like growth factor-1 reverses hypoalgesia and improves mobility in a mouse model of diabetic peripheral neuropathy. - Rat Genome Database

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Systemic Insulin-like growth factor-1 reverses hypoalgesia and improves mobility in a mouse model of diabetic peripheral neuropathy.

Authors: Chu, Q  Moreland, R  Yew, NS  Foley, J  Ziegler, R  Scheule, RK 
Citation: Chu Q, etal., Mol Ther. 2008 Aug;16(8):1400-8. doi: 10.1038/mt.2008.115. Epub 2008 Jun 10.
RGD ID: 8549454
Pubmed: PMID:18545223   (View Abstract at PubMed)
DOI: DOI:10.1038/mt.2008.115   (Journal Full-text)

Peripheral neuropathy is a particularly debilitating complication of both type 1 and type 2 diabetes characterized by sensory and motor neuron damage and decreased circulating levels of insulin-like growth factor 1 (IGF-1). Quite often, an early hyperalgesia is followed by hypoalgesia and muscle weakness. Hypoalgesia can lead to significant morbidity for which there is no current treatment. Hyperglycemic, streptozotocin (STZ)-induced rodent models reproduce these symptoms. We investigated whether increasing systemic IGF-1 could improve neuronal function in hyper- and hypoalgesic STZ-treated mice. Increased circulating levels of IGF-1 were achieved by delivering a plasmid or adeno-associated viral (AAV) vector bearing mouse IGF-1 to the liver. Treating mice in the hyperalgesia stage prevented later hypoalgesia. Treating mice in the hypoalgesia stage reversed existing hypoalgesia. This latter effect could be seen by merely restoring IGF-1 serum levels to normalcy, which was possible to achieve by IGF-1 gene therapy or insulin treatment. Sensory nerve functional correction was seen to be correlated with attenuated Schwann cell vacuolization and demyelination in peripheral sensory nerve fibers. A further increase in serum IGF-1 levels with gene therapy also improved motor function, consistent with the observed prevention of both muscle atrophy and peripheral motor nerve fiber demyelination. These results suggest that the restoration of systemic levels of IGF-1 may prove to be a highly effective therapeutic modality for treating diabetic peripheral neuropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetic neuropathy treatmentISOIgf1 (Mus musculus)8549454; 8549454 RGD 
diabetic neuropathy treatmentIDA 8549454 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information