International Urology and Nephrology

, Volume 49, Issue 11, pp 2079–2086 | Cite as

High glucose stimulates cell proliferation and Collagen IV production in rat mesangial cells through inhibiting AMPK-KATP signaling

  • Bei Zhang
  • Yong-quan ShiEmail author
  • Jun-jie Zou
  • Xiang-fang Chen
  • Wei Tang
  • Fei Ye
  • Zhi-min Liu
Nephrology – Original Paper



The present study investigated the putative mechanisms underlying effects of KATP channel on high glucose (HG)-induced mesangial cell proliferation and tissue inhibitors of metalloproteinases (TIMP)-2 and Collagen IV production.


Rat mesangial cells were subjected to whole cell patch clamp to record the KATP channel currents under high glucose (HG, 30 mM) condition. Cell proliferation was measured using a CCK-8 assay. The production of TIMP-2 and Collagen IV and AMP-activated protein kinase (AMPK)-signaling pathway activity was assessed by ELISA and Western blotting, respectively. AMPK agonist (AICAR) was used to analyze the role of this kinase. The expression of KATP subunit (Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B) was examined using quantitative real-time PCR (RT-PCR).


We found that HG was significant decreases in the expression of Kir6.1, SUB2A and SUB2B, three subunits of KATP, TIMP-2 production, KATP channel activity and AMPK activity, while it promoted the cell proliferation and Collagen IV production in rat mesangial cells. Pretreatment with KATP selective opener (diazoxide, DZX) significantly inhibited HG-induced mesangial cell proliferation, Collagen IV production and decrease in KATP channel activity in rat mesangial cells, which were reversed by pretreatment of 5-hydroxydecanoate, a selective inhibitor of KATP. Moreover, AICAR pretreatment inhibited HG-induced decrease in KATP channel activity.


Taken together, activating AMPK-KATP signaling may protect against HG-induced mesangial cell proliferation and Collagen IV production, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy (DN).


KATP channel AMP-activated protein kinase High glucose Cell proliferation Collagen IV 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Bei Zhang
    • 1
  • Yong-quan Shi
    • 1
    Email author
  • Jun-jie Zou
    • 1
  • Xiang-fang Chen
    • 1
  • Wei Tang
    • 1
  • Fei Ye
    • 1
  • Zhi-min Liu
    • 1
  1. 1.Department of EndocrinologyShanghai Changzheng HospitalShanghaiPeople’s Republic of China

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