Journal of Pharmacological Sciences (Jul 2019)

IRR is involved in glucose-induced endocytosis after insulin secretion

  • Mami Yamaoka,
  • Takeshi Terabayashi,
  • Tomoki Nishioka,
  • Kozo Kaibuchi,
  • Tomohisa Ishikawa,
  • Toshimasa Ishizaki,
  • Toshihide Kimura

Journal volume & issue
Vol. 140, no. 3
pp. 300 – 304

Abstract

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Endocytosis after insulin secretion plays a pivotal role in the regulation of insulin secretion in pancreatic β-cells. Our recent study suggested that EPI64, a GTPase activating protein for Rab27a, contributes to the regulation of glucose-induced endocytosis, which is mediated by the GDP-bound form of Rab27a. Here, we identified insulin receptor-related receptor (IRR) as an EPI64-interacting protein. Knockdown of IRR inhibited glucose-induced uptake of transferrin, a marker of endocytosis, translocation of the guanine-nucleotide-exchange factor ARNO to the plasma membrane, and generation of phosphatidylinositol 3,4,5-trisphosphate (PIP3). These results suggest that IRR functions upstream of PIP3 generation and controls endocytosis after insulin secretion. Keywords: Endocytosis, Insulin, Diabetes