Biology and mechanism of action:


Mitochondrial signalling is essential for activation of insulin receptor in the brain

Mitocholine mechanisms of actionNeuronal insulin receptor isoform IR-A is widely distributed in the brain and binds insulin and insulin like growth factor 2 (IGF2) with a high affinity.

We discovered that mitochondrial signalling is an integral part of the insulin stimulated IR-A autophosphorylation. This signal occurs at times preceding autophosphorylation.

Neurons produce a 20 s spike of H2O2 release in response to insulin.

H2O2 signal generates all-or-nothing condition for IR-A autophosphorylation: autophosphorylation occurs, if H2O2 exceeds a certain threshold or NO autophosphorylation occurs even at highest insulin dose if H2O2 signal does not exceed the threshold. Mitochondrial H2O2 is key for IR-A autophosphorylation.

Mitochondrial complex II is the only source of H2O2 signal. Succinate is the only substrate that supports generation of signalling H2O2 in response to insulin.

Mitocholine improves sensitivity of neuronal insulin receptors to insulin

Mitocholine supports the mitochondrial signalling being a superior succinate donor. It improves the sensitivity of neuronal insulin receptors to insulin.