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FKBP12.6-knockout mice display hyperinsulinemia and resistance to high-fat diet-induced hyperglycemia.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2010 Feb; Vol. 24 (2), pp. 357-63. Date of Electronic Publication: 2009 Oct 05. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Animals
Hyperglycemia prevention & control
Insulin Resistance physiology
Insulin Secretion
Mice
Mice, Knockout
Tacrolimus Binding Protein 1A genetics
Tacrolimus Binding Protein 1A physiology
Blood Glucose metabolism
Dietary Fats adverse effects
Hyperglycemia metabolism
Hyperinsulinism etiology
Insulin metabolism
Tacrolimus Binding Protein 1A deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 19805579
- Full Text :
- https://doi.org/10.1096/fj.09-138446