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[Effect of small interfering RNA-mediated angiotensin II type 1 receptor knockdown on first-phase insulin secretion

Qiuyan Yi1, Yanqing Liu, Zhen Zhang

  • 1Department of Endocrinology, Nanjing Clinical Institute of Nanjing University, Nanjing 210002, China.E-mail: 357660675@qq.com.

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University
|May 29, 2015
PubMed
Abstract

Insights

Knocking down angiotensin II type 1 receptor (AT1R) in db/db mouse islets improved first-phase insulin secretion. This was achieved by up-regulating glucose transporters GLUT-2 and GCK, suggesting a mechanism for AT1R blockers.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Diabetes Research

Background:

  • Type 2 diabetes is characterized by impaired insulin secretion.
  • The renin-angiotensin system, specifically angiotensin II type 1 receptor (AT1R), plays a role in glucose metabolism.
  • db/db mice serve as a model for studying type 2 diabetes and its complications.

Purpose of the Study:

  • To investigate the impact of AT1R knockdown on first-phase insulin secretion in isolated islets from db/db mice.
  • To explore the underlying molecular mechanisms, including the role of GLUT-2 and GCK.

Main Methods:

  • Islet isolation from db/db and db/m mice.
  • Adenoviral-mediated siRNA delivery to knockdown AT1R in islets.
  • Assay of AT1R, GLUT-2, and GCK expression levels.
  • Islet perifusion to assess insulin secretion kinetics.

Main Results:

  • db/db mouse islets exhibited elevated AT1R expression compared to db/m mice.
  • Ad-siAT1R treatment significantly reduced AT1R expression and increased GLUT-2 and GCK levels.
  • First-phase insulin secretion, impaired in control islets, was markedly improved by Ad-siAT1R treatment.

Conclusions:

  • Selective AT1R inhibition in db/db mouse islets restores first-phase insulin secretion.
  • Up-regulation of GLUT-2 and GCK are key mechanisms involved in this restoration.
  • AT1R blockers may improve insulin secretion function through these pathways.

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