The effects of endurance exercise and metformin on memory impairment caused by diabetes

Horm Mol Biol Clin Investig. 2023 Feb 9;44(2):187-197. doi: 10.1515/hmbci-2022-0061. eCollection 2023 Jun 1.


Objectives: Diabetes has a negative effect on learning and memory performance, and it is a risk factor for Alzheimer's disease and dementia development. The present study aims to investigate the effects of two kinds of endurance exercise including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) as well as metformin on impaired memory and learning related to streptozotocin (STZ) induced diabetes in rats.

Methods: Forty adult male rats (250 ± 20 g weight) were divided into five groups (n=8), including control, diabetic, as well as diabetic rats treated with metformin (300 mg/kg), and HIIT (20 m/min), and MICT (15 m/min) exercises. Diabetes was induced by STZ (60 mg/kg, i.p.). Serum glucose concentration and oxidative stress markers (SOD, CAT, thiol, and MDA) in the cortex and hippocampus were determined by colorimetric assay. Behavioral tests were performed with a passive avoidance test.

Results: The diabetic groups treated with metformin and both HIIT, and MICT exercises improved the latency and the staying time in the darkroom and lightroom. The entrance frequency into the darkroom also was restored (p<0.01-p<0.001). In both HIIT and MICT exercises as well as metformin groups the oxidative stress induced by diabetes has been reversed and attenuation of the serum glucose level has been observed compared to non-treated diabetic ones (p<0.05-p<0.001).

Conclusions: The results of the present study revealed both HIIT and MICT exercises had protective effects against oxidative stress and behavioral impairments induced by diabetes and these effects were comparable to the effects of metformin.

Keywords: diabetes; exercise; memory impairment; metformin.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Exercise Therapy
  • Glucose
  • Humans
  • Male
  • Memory Disorders / etiology
  • Memory Disorders / therapy
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Oxidative Stress
  • Rats


  • Metformin
  • Glucose