Related Experiment Video

Updated: Jul 16, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

Regulation of insulin receptor function

J F Youngren1

  • 1Mount Zion Medical Center, Diabetes and Endocrine Research, University of California at San Francisco, San Francisco, CA 94143-1616, USA. jack.youngren@ucsf.edu

Cellular and Molecular Life Sciences : CMLS
|March 10, 2007
PubMed

Insights

Insulin resistance, a key factor in type 2 diabetes and heart disease, stems from impaired insulin signaling. This review examines how insulin receptor (IR) dysfunction, through modifications and inhibiting proteins, disrupts cellular responses.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Endocrinology

Background:

  • Insulin resistance is a major contributor to type 2 diabetes and cardiovascular disease.
  • Impaired insulin signaling, characterized by disrupted cellular phosphorylation events, underlies insulin resistance.
  • The insulin receptor (IR) is central to insulin action and a likely starting point for signaling defects.

Purpose of the Study:

  • To review the mechanisms by which insulin receptor (IR) function is impaired.
  • To explore the role of these IR defects in the development of human diseases.
  • To understand the impact on insulin signaling pathways.

Main Methods:

  • Literature review of studies on insulin signaling and resistance.
  • Analysis of post-translational modifications affecting the insulin receptor.
  • Examination of protein-protein interactions inhibiting insulin receptor activity.

Main Results:

  • Insulin receptor (IR) activation can be hindered by serine phosphorylation and inhibitory proteins (e.g., PC-1, SOCS, Grb).
  • These impairments affect protein conformation and phosphorylation, crucial for signaling.
  • Dysfunctional IR signaling is implicated in various human diseases.

Conclusions:

  • Impaired insulin receptor (IR) function is a critical factor in insulin resistance.
  • Understanding these molecular mechanisms is vital for disease pathogenesis.
  • Further research into IR regulation may offer therapeutic targets.

More Related Videos

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

Related Concept Videos

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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...