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Updated: Mar 28, 2026

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

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Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

Samira Alliouachene1, Benoit Bilanges1, Gaëtan Chicanne2

  • 1UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.

Cell Reports
|December 15, 2015
PubMed

Insights

Class II phosphoinositide 3-kinase-C2β (PI3K-C2β) inhibition enhances insulin sensitivity and glucose tolerance. This finding reveals PI3K-C2β as a potential drug target for metabolic disorders.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Research

Background:

  • The specific roles of class II phosphoinositide 3-kinases (PI3Ks) in organismal functions remain largely undefined, unlike class I PI3Ks.
  • Understanding PI3K-C2β's function is crucial for metabolic disease research.

Purpose of the Study:

  • To investigate the physiological and molecular roles of the kinase activity of PI3K-C2β.
  • To explore PI3K-C2β as a potential therapeutic target for metabolic dysregulation.

Main Methods:

  • Generation and analysis of PI3K-C2β kinase-dead mice.
  • Assessment of insulin sensitivity, glucose tolerance, and liver steatosis.
  • Primary hepatocyte culture and analysis of endosomal trafficking and insulin signaling pathways.

Main Results:

  • PI3K-C2β kinase-dead mice exhibit enhanced insulin sensitivity, improved glucose tolerance, and protection against diet-induced liver steatosis.
  • Systemic inhibition of PI3K-C2β selectively boosts insulin signaling in metabolic tissues.
  • PI3K-C2β inhibition reduces basal phosphoinositide 3-phosphate (PI3P) levels, expands early endosomes, and alters insulin receptor trafficking, amplifying class I PI3K-dependent Akt signaling.

Conclusions:

  • PI3K-C2β is a key regulator of endosomal trafficking impacting insulin signaling.
  • Targeting PI3K-C2β kinase activity offers a promising strategy for enhancing insulin sensitivity and treating metabolic diseases.

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