Autophagy of macrophages is regulated by PI3k/Akt/mTOR signalling in the development of diabetic encephalopathy

Beiyun Wang1, Yuan Zhong1, Qinjie Li1

  • 1Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Aging
|October 23, 2018
PubMed

Insights

Diabetic encephalopathy (DE) involves brain inflammation. PI3k/Akt/mTOR signaling suppresses macrophage autophagy, worsening DE, while inhibiting this pathway may protect against DE.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Endocrinology

Background:

  • Diabetic encephalopathy (DE) is a complication of diabetes, characterized by cognitive decline.
  • Inflammatory macrophages exacerbate DE, whereas macrophage autophagy plays a protective role.
  • The precise molecular mechanisms regulating macrophage autophagy in DE are not fully understood.

Purpose of the Study:

  • To investigate the role of the PI3k/Akt/mTOR/S6K1 signaling pathway in regulating macrophage autophagy during diabetic encephalopathy.
  • To determine the therapeutic potential of modulating this pathway in DE.

Main Methods:

  • Diabetic encephalopathy was induced in rats using streptozotocin (STZ).
  • Macrophage autophagy activity and PI3k/Akt/mTOR/S6K1 signaling were assessed in brain tissue.
  • Rats were treated with an mTOR inhibitor (rapamycin) or an autophagy inhibitor (chloroquine, CQ) to evaluate their effects on DE.

Main Results:

  • Downregulated autophagy and enhanced PI3k/Akt/mTOR/S6K1 signaling were observed in macrophages from STZ-induced diabetic rats.
  • Rapamycin treatment, by inhibiting mTOR, enhanced macrophage autophagy and significantly worsened DE.
  • Chloroquine treatment, by inhibiting autophagy, significantly decreased DE development.

Conclusions:

  • The PI3k/Akt/mTOR/S6K1 signaling pathway appears to promote diabetic encephalopathy by suppressing macrophage autophagy.
  • Targeting this pathway, specifically by enhancing macrophage autophagy, may offer a therapeutic strategy for managing DE.

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