Evidence of Altered Peripheral Nerve Function in a Rodent Model of Diet-Induced Prediabetes

Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of pr...

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Bibliographic Details
Published in:Biomedicines 2020-08, Vol.8 (9), p.313
Main Authors: Hossain, Md Jakir, Kendig, Michael D., Wild, Brandon M., Issar, Tushar, Krishnan, Arun V., Morris, Margaret J., Arnold, Ria
Format: Article
Language:English
Subjects:
Adipose tissue
Blood glucose
Body composition
Cholesterol
Cytokines
Diabetes
Diabetes mellitus
diabetic complications
Diet
Drinking water
Dyslipidemia
Electrodes
Excitability
Fasting
Food processing
Glucose
Glucose tolerance
Inflammation
Insulin
Insulin resistance
Laboratory testing
Lipid metabolism
Mathematical models
Membrane potential
Metabolic disorders
Metabolism
Nerve conduction
nerve excitability
Obesity
Peripheral nerves
Peripheral neuropathy
Phenotyping
prediabetes
Rodents
Triglycerides
Tumor necrosis factor-TNF
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Summary:Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague–Dawley rats (n = 15 CAF versus n = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium–potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines8090313