Related Experiment Video

Updated: May 25, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

T-cadherin attenuates insulin-dependent signalling, eNOS activation, and angiogenesis in vascular endothelial cells

Maria Philippova1, Manjunath B Joshi, Dennis Pfaff

  • 1Laboratory for Signal Transduction, Department of Biomedicine, Basel University Hospital, Hebelstrasse 20, CH 4031 Basel, Switzerland.

Cardiovascular Research
|January 12, 2012
PubMed
Abstract

Insights

T-cadherin (T-cad) negatively regulates insulin signaling in endothelial cells (EC). Increased T-cad impairs insulin

Area of Science:

  • Endocrinology
  • Vascular Biology
  • Cell Signaling

Background:

  • T-cadherin (T-cad) is implicated in vascular disorders, endothelial dysfunction, and insulin resistance.
  • T-cad and insulin share signaling pathways (PI3K/Akt/mTOR) and processes (angiogenesis) in endothelial cells (EC).

Purpose of the Study:

  • To investigate the role of T-cad in regulating insulin signaling and insulin resistance in EC.
  • To determine if T-cad is a determinant of endothelial insulin resistance.

Main Methods:

  • Utilized human EC with stable T-cad overexpression or silencing.
  • Assessed insulin sensitivity by examining insulin signaling cascade effectors, eNOS activation, and angiogenic behavior.
  • Investigated T-cad and insulin receptor (IR) association and localization within lipid rafts.

Main Results:

  • T-cad overexpression attenuated insulin-dependent PI3K/Akt/mTOR signaling, eNOS activation, EC migration, and angiogenesis.
  • T-cad silencing enhanced these insulin-mediated responses.
  • T-cad-mediated inhibition involved Akt/mTOR negative feedback and IR substrate degradation.
  • T-cad and IR interact within lipid rafts; hyperinsulinemia upregulates T-cad.

Conclusions:

  • T-cad expression modulates endothelial cell signaling and functional responses to insulin.
  • Identified a novel mechanism where T-cad up-regulation contributes to endothelial insulin resistance pathogenesis.

More Related Videos

Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies09:03

Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies

Published on: June 30, 2023

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...