Related Experiment Video

Updated: Apr 19, 2026

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
09:48

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

Published on: February 17, 2023

3.8K

Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic

Sona Kang1, Linus T Tsai1, Yiming Zhou1

  • 1Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

Nature Cell Biology
|December 16, 2014
PubMed

Insights

This study reveals common molecular pathways underlying insulin resistance, a key feature of Type 2 diabetes (T2D). Identifying shared transcriptional and epigenomic signatures helps uncover pathogenic mechanisms in conditions like obesity and aging.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Insulin resistance is central to Type 2 diabetes (T2D) and linked to obesity, aging, and steroid use.
  • The shared molecular basis for insulin resistance across diverse conditions remains poorly understood.
  • Transcriptional and epigenetic factors are implicated but not fully characterized.

Purpose of the Study:

  • To compare cell-autonomous models of insulin resistance induced by tumor necrosis factor-alpha and dexamethasone.
  • To generate detailed transcriptional and epigenomic maps of cellular insulin resistance.
  • To identify common mediators and molecular signatures of insulin resistance.

Main Methods:

  • Comparative analysis of cell models.
  • Transcriptional profiling.
  • Epigenomic mapping.
  • Gain- and loss-of-function studies.

Main Results:

  • Detailed transcriptional and epigenomic maps of cellular insulin resistance were constructed.
  • Glucocorticoid receptor and vitamin D receptor were identified as common mediators.
  • A common molecular signature for cellular insulin resistance was defined.

Conclusions:

  • Common transcriptional and epigenomic pathways contribute to insulin resistance.
  • This signature aids in identifying pathogenic mechanisms across various clinical conditions.
  • The findings provide insights into the molecular basis of T2D and related disorders.

More Related Videos

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

11.0K
Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay08:34

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay

Published on: July 15, 2025

798

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.5K
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...
6.4K
Intracellular Hormone Receptors01:08

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
63.4K
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
13.2K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.7K
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
6.6K