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Endocrine

, Volume 63, Issue 1, pp 70–78 | Cite as

Sitagliptin improves renal function in diabetic nephropathy in male Sprague Dawley rats through upregulating heme oxygenase-1 expression

  • Jianping WangEmail author
  • Lan Hu
  • Yang Chen
  • Ting Fu
  • Tao Jiang
  • Aihua Jiang
  • Xiaoxing You
Original Article

Abstract

Purpose

Oxidative stress is an important mechanism for diabetic nephropathy. Studies showed that hemo oxygenase-1 (HO-1) expression in renal tissue of patients with diabetic nephropathy has upregulated, while the HO-1 can protect the body through anti-oxidative stress. The study aimed to preliminarily explore the molecular mechanism by observing the effect of Sitagliptin on HO-1 expression in renal tissue of rats with diabetic nephropathy.

Methods

The diabetic nephropathy rat model was established by STZ injection followed by intraperitoneal injection of sitagliptin with different concentrations. The mRNA expressions of HO-1 were detected by real-time PCR and Western blot and HO-1 enzyme activity change was detected by colorimetry. Human renal mesangial cell (HRMC) were cultured in vitro with high glucose concentration (30 μmol/L), phosphatidylinositol-3-kinase (PI3K) level and nuclear factor erythroid-2-related factor (Nrf2) content in cytoplasm and cell nucleus were observed before and after treatment with sitagliptin, as well as the action of in meditating HO-1 expression.

Results

HO-1 mRNA, protein level, and HO-1 enzyme activity in renal tissue of rats with diabetic nephropathy were significantly increased after treatment with sitagliptin (P < 0.05). As comparison, the 24 h urinary microalbumin, creatinine, and boold urea nitrogen were all decreased after treatment of sitagliptin (P < 0.05). Similar results were observed after CoPP (an agonist of HO-1) treatment (P < 0.05). In contrast, ZnPP, an inhibitor of HO-1, significantly abrogated the inhibitory effect of sitagliptin (P < 0.05). Phosphorylation of PI3K and Nrf2 nuclear translocation under high-glucose concentration condition was induced by sitagliptin in HRMC. HO-1 expression was suppressed by pretreating HRMC with PI3K inhibitor or RNA interference.

Conclusions

Sitagliptin may induce HO-1 expression via activation of PI3K and Nrf2 in rats with diabetic nephropathy; HO-1 can improve the oxidative stress of diabetic nephropathy, eventually protect from diabetic nephropathy.

Keywords

Sitagliptin Heme oxygenase-1 Diabetic nephropathy Phosphoinositide 3-kinase Nuclear factor erythroid-2 related factor (Nrf2) Phosphatidylinositol-3-kinase (PI3K) 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jianping Wang
    • 1
    Email author
  • Lan Hu
    • 1
    • 2
  • Yang Chen
    • 1
  • Ting Fu
    • 1
  • Tao Jiang
    • 1
  • Aihua Jiang
    • 1
  • Xiaoxing You
    • 3
  1. 1.Department of EndocrinologyThe Second Affiliated Hospital of University of South ChinaHengyangChina
  2. 2.Department of EndocrinologyThe First people’s Hospital of Xiangtan CityXiangtanChina
  3. 3.University of South ChinaHengyangChina

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