title: T-cadherin (Cdh13) in association with pancreatic β-cell granules contributes to second phase insulin secretion.
abstract: 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 β-cells. Immunohistochemistry and electron microscopy of islets in situ and targeting of RFP-tagged T-cadherin to GFP-labeled insulin granules in isolated β-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 KCl-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 β-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.
authors: Sanford-Burnham Medical Research Institute, Orlando, FL, USA. btyrberg@sanfordburnham.org
authors: Björn
authors: B
authors: Tyrberg
authors: Philip
authors: P
authors: Miles
authors: Krist T
authors: KT
authors: Azizian
authors: Martin S
authors: MS
authors: Denzel
authors: Maria L
authors: ML
authors: Nieves
authors: Edward Z
authors: EZ
authors: Monosov
authors: Fred
authors: F
authors: Levine
authors: Barbara
authors: B
authors: Ranscht
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin; D007328:Insulin