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Insulin: The Receptor and Signaling Pathways

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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...

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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

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Related Experiment Video

Updated: Jul 6, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

Insulin receptor knock-out mice.

¹Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892USA.

Trends in Endocrinology and Metabolism: TEM

|April 1, 1997

Summary

Targeted mutations in the insulin receptor gene of mice produced surprising outcomes. This research explores how this animal model enhances understanding of insulin action and non-insulin-dependent diabetes mellitus.

Area of Science:

Endocrinology
Metabolism
Genetics

Background:

The insulin receptor is crucial for glucose homeostasis.
Understanding insulin resistance is key to treating diabetes.
Mouse models are vital for studying complex biological pathways.

Purpose of the Study:

To review findings from targeted mutagenesis of the insulin receptor gene in mice.
To analyze the utility of this animal model for studying insulin action.
To investigate the role of insulin receptor mutations in non-insulin-dependent diabetes mellitus.

Main Methods:

Targeted mutagenesis of the insulin receptor gene in mice.
Review of recent experimental findings.
Analysis of the resulting phenotypes and their implications.

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Last Updated: Jul 6, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

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

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Published on: July 15, 2025

Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets

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Published on: May 11, 2015

Main Results:

Mutagenesis yielded unexpected results regarding insulin receptor function.
The mouse model provides insights into insulin signaling pathways.
Observed alterations correlate with aspects of impaired insulin action.

Conclusions:

Targeted mutagenesis in mice is a powerful tool for dissecting insulin receptor function.
This model advances our comprehension of insulin resistance mechanisms.
Findings contribute to understanding the pathophysiology of non-insulin-dependent diabetes mellitus.