FKBP12.6 disruption impairs glucose-induced insulin secretion

Naoya Noguchi, Takeo Yoshikawa, Takayuki Ikeda, Iwao Takahashi, Nausheen Jamal Shervani, Akira Uruno, Akiyo Yamauchi, Koji Nata, Shin Takasawa, Hiroshi Okamoto, Akira Sugawara

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Cyclic ADP-ribose (cADPR), accumulated in pancreatic β-cells in response to elevated ATP levels after glucose stimulation, mobilizes Ca2+ from the endoplasmic reticulum through the ryanodine receptor (RyR) and thereby induces insulin secretion. We have recently demonstrated in an in vitro study that cADPR activates RyR through binding to FK506-binding protein 12.6 (FKBP12.6), an accessory protein of RyR. Here we generated FKBP12.6-deficient (FKBP12.6-/-) mice by homologous recombination. FKBP12.6-/- mice showed glucose intolerance coupled to insufficient insulin secretion upon a glucose challenge. Insulin secretion in response to glucose was markedly impaired in FKBP12.6-/- islets, while sulfonylurea- or KCl-induced insulin secretion was unaffected. No difference was found in the glucose oxidation rate between FKBP12.6-/- and wild-type islets. These results indicate that FKBP12.6 plays a role in glucose-induced insulin secretion downstream of ATP production, independently of ATP-sensitive K+ channels, in pancreatic β-cells.

Original languageEnglish
Pages (from-to)735-740
Number of pages6
JournalBiochemical and biophysical research communications
Issue number4
Publication statusPublished - 2008 Jul 11


  • Cyclic ADP-ribose
  • FKBP12.6
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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