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FKBP12.6‐knockout mice display hyperinsulinemia and resistance to high‐fat diet‐induced hyperglycemia
Author(s) -
Chen Zheng,
Li Zhengzheng,
Wei Bin,
Yin Wenxuan,
Xu Tao,
Kotlikoff Michael I.,
Ji Guangju
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-138446
Subject(s) - hyperinsulinemia , endocrinology , medicine , insulin resistance , knockout mouse , insulin , diabetes mellitus , type 2 diabetes , islet , chemistry , biology , receptor
FK506 binding protein 12.6 kDa (FKBP12.6), a protein that regulates ryanodine Ca 2+ release channels, may act as an important regulator of insulin secretion. In this study, the role of FKBP12.6 in the control of insulin secretion and blood glucose is clarified using FKBP12.6 −/− mice. FKBP12.6 −/− mice showed significant fed hyperinsulinemia but exhibited normoglycemia, fasting normoinsulinemia, and normal body weight compared with wild‐type (WT) littermate control mice. Deletion of FKBP12.6 resulted in enhanced glucose‐stimulated insulin secretion (GSIS) both in vivo and in vitro , a result that is due to enhanced glucose‐induced islet Ca 2+ elevation. After a high‐fat dietary challenge (HF diet) for 3 mo, FKBP12.6 −/− mice displayed higher body weight, hyperinsulinemia, and lower fed blood glucose concentrations compared with WT mice. FKBP12.6 −/− mice displayed hyperinsulinemia, and resistance to HF diet‐induced hyperglycemia, suggesting that FKBP12.6 plays an important role in insulin secretion and blood glucose control, and raising the possibility that it may be a potential therapeutic target for the treatment of type 2 diabetes.—Chen, Z., Li, Z., Wei, B., Yin, W., Xu, T., Kotlikoff, M. I., Ji, G. FKBP12.6‐knockout mice display hyperinsulinemia and resistance to high‐fat diet‐induced hyperglycemia. FASEB J . 24, 357–363 (2010). www.fasebj.org