Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes

Koji Okamoto, Naoko Iwasaki, Kent Doi, Eisei Noiri, Yasuhiko Iwamoto, Yasuko Uchigata, Toshiro Fujita, Katsushi Tokunaga

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Potassium inwardly rectifying channel, subfamily J, member 15 (KCNJ15) is a type 2 diabetes-associated risk gene, and Kcnj15 overexpression suppresses insulin secretion in rat insulinoma (INS1) cells. The aim of the current study was to characterize the role of Kcnj15 by knockdown of this gene in vitro and in vivo. Human islet cells were used to determine the expression of KCNJ15. Expression of KCNJ15 mRNA in islets was higher in subjects with type 2 diabetes. In INS1 cells, Kcnj15 expression was induced by high glucose-containing medium. Regulation of Kcnj15 by glucose and its effect on insulin secretion were analyzed in INS1 cells and in normal mice and diabetic mice by the inactivation of Kcnj15 using small interfering RNA. Knockdown of Kcnj15 increased the insulin secretion in vitro and in vivo. KCNJ15 and Ca 2+-sensing receptor (CsR) interact in the kidney. Binding of Kcnj15 with CsR was also detected in INS1 cells. In conclusion, downregulation of Kcnj15 leads to increased insulin secretion in vitro and in vivo. The mechanism to regulate insulin secretion involves KCNJ15 and CsR.

Original languageEnglish
Pages (from-to)1734-1741
Number of pages8
JournalDiabetes
Volume61
Issue number7
DOIs
Publication statusPublished - 2012 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes'. Together they form a unique fingerprint.

  • Cite this

    Okamoto, K., Iwasaki, N., Doi, K., Noiri, E., Iwamoto, Y., Uchigata, Y., Fujita, T., & Tokunaga, K. (2012). Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes. Diabetes, 61(7), 1734-1741. https://doi.org/10.2337/db11-1201