Insulin enhances mitochondrial inner membrane potential and increases ATP levels through phosphoinositide 3-kinase in adult sensory neurons

Tze-Jen Huang, Alex Verkhratsky, Paul Fernyhough

    Research output: Contribution to journalArticle

    103 Citations (Scopus)

    Abstract

    We tested the hypothesis that neurotrophic factors control neuronal metabolism by directly regulating mitochondrial function in the absence of effects on survival. Real-time whole cell fluorescence video microscopy was utilized to analyze mitochondrial inner membrane potential (Δψ m), which drives ATP synthesis, in cultured adult sensory neurons. These adult neurons do not require neurotrophic factors for survival. Insulin and other neurotrophic factors increased Δψ m 2-fold compared with control over a 6- to 24-h period (P < 0.05). Insulin modulated Δψ m by activation of the phosphoinositide 3-kinase (PI 3-K) pathway. Insulin also induced rapid and long-term (30 h) PI 3-K-dependent phosphorylation of Akt and cAMP response element binding protein (CREB). Additionally, insulin elevated the redox state of the mitochondrial NAD(P)H pool, increased hexokinase activity (first committed step of glycolysis), and raised ATP levels. This study demonstrates that insulin utilizes the PI 3-K/Akt pathway to augment ATP synthesis that we propose contributes to the energy requirement for neurotrophic factor-driven axon regeneration.

    Original languageEnglish
    Pages (from-to)42-54
    Number of pages13
    JournalMolecular and Cellular Neuroscience
    Volume28
    Issue number1
    Early online date28 Oct 2004
    DOIs
    Publication statusPublished - Jan 2005

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