期刊
ISLETS
卷 3, 期 6, 页码 327-337出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/isl.3.6.17705
关键词
T-cadherin; adiponectin; islets of Langerhans; exocytosis; secretion; glucose homeostasis; electron microscopy; confocal microscopy; hyperglycemic clamp
资金
- National Institute of Health [HL102680]
- NIDDK [DK0889059]
- Larry L. Hillblom Foundation
Glucose homeostasis depends on adequate control of insulin secretion. We report the association of the cell-adhesion and adiponectin (APN)-binding glycoprotein T-cadherin (Cdh13) with insulin granules in mouse and human beta-cells. Immunohistochemistry and electron microscopy of islets in situ and targeting of RFP-tagged T-cadherin to GFP-labeled insulin granules in isolated beta-cells demonstrate this unusual location. Analyses of T-cadherin-deficient (Tcad-KO) mice show normal islet architecture and insulin content. However, T-cadherin is required for sufficient insulin release in vitro and in vivo. Primary islets from Tcad-KO mice were defective in glucose induced but not KCI-mediated insulin secretion. In vivo, second phase insulin release in T-cad-KO mice during a hyperglycemic clamp was impaired while acute first phase release was unaffected. Tcad-KO mice showed progressive glucose intolerance by 5 mo of age without concomitant changes in peripheral insulin sensitivity. Our analyses detected no association of APN with T-cadherin on beta-cell granules although colocalization was observed on the pancreatic vasculature. These data identify T-cadherin as a novel component of insulin granules and suggest that T-cadherin contributes to the regulation of insulin secretion independently of direct interactions with APN.
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