Title:Treatment for Diabetic Peripheral Neuropathy: What have we Learned
from Animal Models?
Volume: 18
Issue: 5
Author(s): Mark Yorek*
Affiliation:
- Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242 USA
- Department of Veterans Affairs
Iowa City Health Care System, Iowa City, IA, 52246 USA
- Fraternal Order of Eagles Diabetes Research Center, University
of Iowa, Iowa City, IA, 52242 USA
Keywords:
Diabetes, diabetic neuropathy, hyperglycemia, hyperlipidemia, insulin resistance, and animal models.
Abstract:
Introduction: Animal models have been widely used to investigate the etiology and potential
treatments for diabetic peripheral neuropathy. What we have learned from these studies and
the extent to which this information has been adapted for the human condition will be the subject
of this review article.
Methods: A comprehensive search of the PubMed database was performed, and relevant articles
on the topic were included in this review.
Results: Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral
neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and
the microvasculature, which contribute to the phenotypic nature of this most common complication
of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral
neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being
the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in
type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater
role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral
neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation.
However, continuing research has identified numerous other potential factors that may contribute
to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation
of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition,
recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal
models, representing pre-diabetes in the absence of hyperglycemia.
Conclusion: This complexity complicates the successful treatment of diabetic peripheral neuropathy,
and results in the poor outcome of translating successful treatments from animal studies to human
clinical trials.