Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

Laura J Andreasen1,2, Rikke K Kirk2, Christian Fledelius2

  • 1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.

Abstract

Insights

High-dose insulin treatment in a type 2 diabetes rat model attenuated nerve damage, but did not fully prevent diabetic peripheral neuropathy (DPN). Poor glycemic control and dyslipidemia also contribute to DPN progression.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Metabolic Diseases

Background:

  • Clinical guidelines for diabetic peripheral neuropathy (DPN) management focus on glycemic control, but its preventive effect in type 2 diabetes (T2D) is limited.
  • DPN development in T2D patients requires further investigation into underlying causes beyond hyperglycemia.

Purpose of the Study:

  • To investigate the effect of insulin treatment on DPN development in a rat model of T2D.
  • To assess the role of glycemic control and dyslipidemia in DPN progression.

Main Methods:

  • Male Sprague-Dawley rats were fed a high-fat diet and induced with streptozotocin to model T2D.
  • Diabetic rats received no insulin, low-dose, or high-dose insulin treatment for 12 weeks.
  • Neuropathy was assessed using Hargreaves' test and intraepidermal nerve fiber density; blood parameters and sorbitol levels were also measured.

Main Results:

  • Insulin treatment dose-dependently reduced blood glucose and lipids, and increased body fat.
  • High-dose insulin attenuated small nerve fiber damage compared to untreated and low-dose groups.
  • Glycemic status, circulating lipids, and sciatic nerve sorbitol levels were negatively associated with nerve fiber damage.

Conclusions:

  • High-dose insulin treatment can attenuate DPN-related small nerve fiber damage in T2D rats.
  • Both poor glycemic control and dyslipidemia are linked to DPN progression.
  • This T2D rat model is suitable for preclinical research on DPN treatment opportunities.

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