Determination of peripheral neuropathy in high‐fat diet fed low‐dose streptozotocin‐treated female C57Bl/6J mice and Sprague–Dawley rats

AIMS/INTRODUCTION: Peripheral neuropathy is a common complication of diabetes and also occurs in 30% of human obese individuals with impaired glucose tolerance. Even though peripheral neuropathy affects both sexes, most pre‐clinical studies have been carried out using male rodents. The aim of the present study was to create diet‐induced obesity and type 2 diabetes in female rats and mice in order to examine the development of peripheral neuropathy. MATERIALS AND METHODS: At 12 weeks‐of‐age, rats and mice were separated into three groups. Two groups or rats and mice were fed a 60‐kcal% high‐fat diet for 12 weeks (rats) or 8 weeks (mice). To induce type 2 diabetes, one group of high‐fat diet‐fed rats and mice were treated with a low dose of streptozotocin. Analyses of multiple neural end‐points were carried out 12 weeks later. RESULTS: Glucose utilization was impaired in diet‐induced obese female rats and mice, as was a number of neurological end‐points including nerve conduction velocity, intraepidermal and subepithelial corneal nerve fiber densities, and thermal and mechanical sensitivity. When female diet‐induced obese rats or mice were made hyperglycemic, glucose utilization and sensory nerve density of the skin and cornea, as well as thermal and mechanical sensitivity, were more significantly impaired compared with diet‐induced obese female rodents. CONCLUSIONS: These studies show that diet‐induced obese and type 2 diabetic female rodents develop peripheral neuropathy that is similar to that occurring in male rodents. However, for female rats, more aggressive treatment is required to induce dietary obesity.