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    Actovegin mimics insulin, inhibits pdk stimulates pdh

    Scheduled Pinned Locked Moved Literature Review
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      user73636
      last edited by user73636

      Inositol phosphoglycans (IPGs) from Actovegin create a "push-pull" switch on PDH that ramps up glucose burning. They push PDH "on" by activating the phosphatase (PDP) while pulling it "off-limits" by blocking the kinase (PDK)

      Simple Push-Pull Breakdown
      Push (Activate PDH): IPGs turn on PDP, a phosphatase that removes phosphate tags from PDH—making it active so pyruvate from glucose flows into energy production.

      Pull
      (Block Shutdown): IPGs inhibit PDK, the kinase that adds those phosphate tags to shut PDH down. This sigmoidal block kicks in sharply at normal doses, preventing re-inactivation.
      Key Studies
      1990 Actovegin/IPG Study: Isolated IP-oligosaccharides from Actovegin showed partial insulin-mimetic effects on glucose uptake in fat cells (30% of insulin's effect) via carrier activation—without translocation—implying downstream PDH enhancement.

      2008 Biochemical Journal: Defined the "push-pull" mechanism where IPG-P activates PDP linearly while inhibiting PDK sigmoidally, shifting PDC to active state;

      Linear PDP Activation: IPG-P stimulates pyruvate dehydrogenase phosphatase (PDP) activity in a straight-line dose-response, dephosphorylating PDH to its active form.Sigmoidal PDK Inhibition: IPG-P potently blocks PDK with a sharp Hill coefficient (n=3.8), creating a switch-like cutoff that prevents PDH re-phosphorylation at physiological concentrations (~10 nM).Net Effect: 2-3x increase in active PDH, shifting pyruvate flux to acetyl-CoA/TCA cycle vs. lactate—mimicking insulin's effect on glucose oxidation

      Glucose Oxidation Link
      These IPGs boost PDH activity ~2-3x under physiological doses, channeling pyruvate to acetyl-CoA/TCA instead of lactate.

      Actovegin shows insulin-mimetic effects that stimulate pyruvate dehydrogenase (PDH) activity, primarily through inositolphosphooligosaccharides (IPOs) derived from calf blood extract. These effects mimic insulin's stimulation of glucose transport, PDH activation, and glucose oxidation
      Actovegin, a calf blood extract, contains inositol phosphooligomansides (IPO) that enhance glucose uptake independently of insulin, activating transporters up to 50% of insulin's maximum effect

      Stacking this with meldonium or other pro metabolic pro glucose oxidation substances could be pretty big.

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