Related Experiment Video

Updated: Aug 21, 2026

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization
08:13

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization

Published on: May 18, 2020

Inhibition of insulin-like growth factor I receptor tyrosine kinase by ethanol

Raphael Rubin1, Rob Harrison, Xian-Feng Chen

  • 1Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, 226 Alumni Hall, Philadelphia, PA 19107, USA. raphael.rubin@jefferson.edu

Biochemical Pharmacology
|October 13, 2004
PubMed

Insights

Ethanol directly inhibits insulin and IGF-I receptor tyrosine kinases, preventing their initial activation. This molecular mechanism explains how alcohol impairs cell growth and survival signaling pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Signaling

Background:

  • Ethanol disrupts insulin and insulin-like growth factor-I (IGF-I) signaling, impacting cell growth and survival.
  • This disruption is linked to the inhibition of insulin receptor (IR) and IGF-I receptor (IGF-IR) autophosphorylation.

Purpose of the Study:

  • To investigate the direct molecular mechanisms by which ethanol inhibits IR and IGF-IR tyrosine kinases.
  • To elucidate the interaction of ethanol with the kinase domains of IR and IGF-IR.

Main Methods:

  • Computer modeling of ethanol interaction with IR and IGF-IR kinase domains.
  • Biochemical assays using purified IGF-IR kinase (IGF-IRK) to assess ethanol's effect on phosphorylation.
  • Experiments in cerebellar granule neurons to study ethanol's impact on IGF-IR autophosphorylation.

Main Results:

  • Computer modeling predicted ethanol binding within the kinase activation cleft of IR and IGF-IR.
  • Ethanol inhibited peptide substrate phosphorylation by non-phosphorylated IGF-IRK but not by autophosphorylated IGF-IRK.
  • Ethanol inhibited IGF-IRK autophosphorylation and apo-IGF-IR autophosphorylation in neurons, but did not reverse IGF-I-stimulated phosphorylation.

Conclusions:

  • Ethanol directly inhibits IGF-IR tyrosine kinase activity.
  • Ethanol's inhibitory effect occurs during the initial activation phase by preventing kinase activation loop engagement.
  • These findings provide a molecular basis for ethanol's detrimental effects on insulin and IGF-I signaling pathways.

More Related Videos

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer08:37

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer

Published on: November 15, 2024

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...
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...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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 DNA...