Activation of protein kinase C-ζ in pancreatic β-cells in vivo improves glucose tolerance and induces β-cell expansion via mTOR activation Academic Article uri icon


MeSH Major

  • Glucose Intolerance
  • Insulin-Secreting Cells
  • Protein Kinase C
  • TOR Serine-Threonine Kinases


  • TG mice displayed increased plasma insulin, improved glucose tolerance, and enhanced insulin secretion with concomitant upregulation of islet insulin and glucokinase expression. In addition, TG mice displayed increased β-cell proliferation, size, and mass compared with wild-type littermates. The increase in β-cell proliferation was associated with upregulation of cyclins D1, D2, D3, and A and downregulation of p21. Phosphorylation of D-cyclins, known to initiate their rapid degradation, was reduced in TG mouse islets. Phosphorylation/inactivation of GSK-3β and phosphorylation/activation of mTOR, critical regulators of D-cyclin expression and β-cell proliferation, were enhanced in TG mouse islets, without changes in Akt phosphorylation status. Rapamycin treatment in vivo eliminated the increases in β-cell proliferation, size, and mass; the upregulation of cyclins Ds and A in TG mice; and the improvement in glucose tolerance-identifying mTOR as a novel downstream mediator of PKC-ζ-induced β-cell replication and expansion in vivo. CONCLUSIONS PKC:-ζ, through mTOR activation, modifies the expression pattern of β-cell cycle molecules leading to increased β-cell replication and mass with a concomitant enhancement in β-cell function. Approaches to enhance PKC-ζ activity may be of value as a therapeutic strategy for the treatment of diabetes.

publication date

  • October 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3178296

Digital Object Identifier (DOI)

  • 10.2337/db10-1783

PubMed ID

  • 21911744

Additional Document Info

start page

  • 2546

end page

  • 59


  • 60


  • 10