Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The CRUMB study: closed-loop response to unannounced mixed and carbohydrates-rich breakfasts. A randomized controlled crossover pilot-study in a cohort of adolescents with type 1 diabetes.

Endocrine·2026
Same author

Diabetic gastroparesis: pathophysiology and impact on insulin timing choices.

Endocrine·2026
Same author

Validation of the Italian version of the hypoparathyroidism patient questionnaire-28 (HPQ-28): a multicenter study.

Journal of endocrinological investigation·2026
Same author

Treatment with long-acting growth hormone: effectiveness and safety.

Frontiers in endocrinology·2026
Same author

Dyslipidemias associated with endocrine disorders: a position statement of the working group of the nutrition hormones and metabolism club of the italian society of endocrinology (SIE).

Journal of endocrinological investigation·2026
Same author

Comprehensive evaluation of TIR 3B thyroid nodules: Clinical, Ultrasonographical and Cytological features for prediction of malignancy.

Endocrine·2026

Related Experiment Video

Updated: Jun 25, 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

c-Abl and insulin receptor signalling.

Marco Genua1, Giuseppe Pandini, Maria Francesca Cassarino

  • 1Department of Internal Medicine, University of Catania, Catania, Italy.

Vitamins and Hormones
|March 3, 2009
PubMed
Summary

The cytoplasmic tyrosine kinase c-Abl influences the Insulin Receptor's (IR) function, switching it from metabolic to mitogenic effects. Inhibiting c-Abl promotes IR-mediated cell proliferation and migration.

More Related Videos

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay
08:34

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

Published on: July 15, 2025

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
08:47

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

Related Experiment Videos

Last Updated: Jun 25, 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

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay
08:34

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

Published on: July 15, 2025

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
08:47

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Insulin Receptor (IR) and IGF-I receptor (IGF-IR) are homologous but have distinct metabolic and mitogenic functions, respectively.
  • Under certain conditions (e.g., fetal growth, cancer, diabetes), IR can exhibit non-metabolic effects like proliferation and migration.
  • Mechanisms for IR's functional switch include ligand/receptor overexpression, isoform expression, and substrate recruitment.

Purpose of the Study:

  • To investigate the role of cytoplasmic tyrosine kinase c-Abl in the functional switch of the Insulin Receptor (IR).
  • To elucidate the molecular mechanisms by which c-Abl influences IR signaling pathways, differentiating between metabolic and mitogenic outcomes.

Main Methods:

  • Utilized c-Abl inhibition with STI571 in cellular models.
  • Assessed effects on insulin-induced phosphorylation of Akt/GSK-3beta and ERK.
  • Evaluated insulin's impact on glycogen synthesis, cell proliferation, and migration.
  • Employed Abl-null and c-Abl-reconstituted cells to confirm specificity.
  • Investigated the role of focal adhesion kinase (FAK) by examining its phosphorylation status and using FAK-deficient cells.

Main Results:

  • c-Abl is activated by insulin and shares substrates with IR.
  • Inhibition of c-Abl by STI571 attenuated insulin's metabolic effects (Akt/GSK-3beta phosphorylation, glycogen synthesis) but enhanced mitogenic effects (ERK activation, proliferation, migration).
  • These effects were specific to c-Abl and dependent on focal adhesion kinase (FAK) activity, as insulin signaling shifted towards FAK phosphorylation upon c-Abl inhibition.

Conclusions:

  • Insulin-induced c-Abl activation, modulated by FAK, plays a critical role in directing the Insulin Receptor towards either mitogenic or metabolic signaling pathways.
  • c-Abl acts as a key regulator in the functional plasticity of the Insulin Receptor, influencing cellular processes beyond metabolism.