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Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
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Published on: June 25, 2012

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Rictor/mTORC2 is essential for maintaining a balance between beta-cell proliferation and cell size

Yanyun Gu1, Jill Lindner, Anil Kumar

  • 1Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Diabetes
|January 27, 2011
PubMed
Abstract

Insights

Mammalian target of rapamycin complex 2 (mTORC2) signaling is crucial for maintaining pancreatic beta-cell mass and function. Its absence impairs glucose homeostasis, while its interaction with PI3K/AKT pathway balances beta-cell proliferation and size.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Metabolic Signaling

Background:

  • The phosphotidylinositol-3-kinase (PI3K)/mammalian target of rapamycin complex 2 (mTORC2)/AKT signaling pathway regulates critical cellular processes.
  • mTORC2, a key component of this pathway, is implicated in cell growth and survival, but its specific role in pancreatic beta-cell mass and function requires elucidation.

Purpose of the Study:

  • To investigate the role of Rictor, an essential component of mTORC2, in regulating pancreatic beta-cell mass and function.
  • To determine the impact of deleting Rictor and/or Pten on beta-cell proliferation, mass, and glucose homeostasis.

Main Methods:

  • Generation of mice with beta-cell-specific deletions of Rictor or Pten.
  • Analysis of beta-cell mass, proliferation, insulin content, and glucose-stimulated insulin secretion.
  • Assessment of AKT phosphorylation (S473 and T308) and key protein expression (FoxO1, p27).

Main Results:

  • Rictor deletion in beta-cells reduced beta-cell mass, proliferation, and insulin secretion, leading to hyperglycemia and glucose intolerance.
  • Pten deletion increased beta-cell mass through enhanced proliferation and cell size.
  • Mice lacking both Rictor and Pten had normal beta-cell mass but larger cells, with increased AKT-T308 phosphorylation despite reduced proliferation.

Conclusions:

  • PI3K/AKT signaling via mTORC2 (specifically pAKT-S473) is vital for maintaining normal beta-cell mass.
  • Phosphorylation of AKT-S473 negatively regulates AKT-T308 phosphorylation, balancing beta-cell proliferation and cell size in response to stimuli.

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