Journal
DISEASE MODELS & MECHANISMS
Volume 11, Issue 12, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.037374
Keywords
Mouse models; Obesity; Peripheral neuropathy; Prediabetes; Type 2 diabetes
Categories
Funding
- National Institutes of Health [1DP3DK094292, 1R24082841]
- Novo Nordisk Foundation Center for Basic Metabolic Research [NNF14degreesC0011633]
- Nathan and Rose Milstein Research Fund
- Sinai Medical Staff Foundation Neuroscience Scholar Fund [2]
- Robert C Graham Fund
- Walbridge Aldinger Graduate Fellowship Fund
- American Diabetes Association [7-12-BS-045]
- Program for Neurology Research Discovery
- A. Alfred Taubman Medical Research Institute
- NIH [DK059637, DK020593, DK059630]
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Peripheral neuropathy (neuropathy) is a common complication of obesity and type 2 diabetes in children and adolescents. To model this complication in mice, 5-week-old male C57BU6J mice were fed a high-fat diet to induce diet-induced obesity (DIO), a model of prediabetes, and a cohort of these animals was injected with low-dose streptozotocin (STZ) at 12 weeks of age to induce hyperglycemia and type 2 diabetes. Neuropathy assessments at 16, 24 and 36 weeks demonstrated that DIO and DIO-STZ mice displayed decreased motor and sensory nerve conduction velocities as early as 16 weeks, hypoalgesia by 24 weeks and cutaneous nerve fiber loss by 36 weeks, relative to control mice fed a standard diet. Interestingly, neuropathy severity was similar in DIO and DIO-STZ mice at all time points despite significantly higher fasting glucose levels in the DIO-STZ mice. These mouse models provide critical tools to better understand the underlying pathogenesis of prediabetic and diabetic neuropathy from youth to adulthood, and support the idea that hyperglycemia alone does not drive early neuropathy. This article has an associated First Person interview with the first author of the paper.
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