Aerobic Exercise Improves Type 2 Diabetes Mellitus-Related Cognitive Impairment by Inhibiting JAK2/STAT3 and Enhancing AMPK/SIRT1 Pathways in Mice

Dis Markers. 2022 May 5:2022:6010504. doi: 10.1155/2022/6010504. eCollection 2022.

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent risk factor for cognitive impairment. Aerobic exercise can improve T2DM-related cognitive impairment; however, the possible mechanisms remain elusive. Thus, we assessed db/m mice and leptin receptor-deficient (db/db) mice that did or did not perform aerobic exercise (8 m/min, 60 min/day, and 5 days/week for 12 weeks). In this study, cognitive function was significantly impaired in the T2DM mice; aerobic exercise improved cognitive impairment through activating the AMPK/SIRT1 signalling pathway and inhibiting the JAK2/STAT3 signalling pathway in T2DM mice. However, after the application of RO8191 (JAK2 activator) or Compound C (AMPK inhibitor), the positive improvement of the exercise was evidently suppressed. Taken together, our data indicated that long-term aerobic exercise improves type 2 diabetes mellitus-related cognitive impairment by inhibiting JAK2/STAT3 and enhancing AMPK/SIRT1 pathways in mice.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cognitive Dysfunction* / etiology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Janus Kinase 2 / metabolism
  • Mice
  • Physical Conditioning, Animal*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 2
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1