How does insulin decrease Phosphofructokinase-2 (PFK2) stimulation?

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From the Research

Insulin decreases PFK2 stimulation by promoting its dephosphorylation through activation of protein phosphatases, as suggested by the study 1. When insulin binds to its receptor, it activates a signaling cascade that does not involve changes in cAMP and effector levels or inhibition of cAMP-dependent protein kinase dissociation, as shown in the study 1. Instead, insulin may act via activation of PFK 2 phosphatase, which leads to the dephosphorylation and inactivation of PFK2. This mechanism is particularly important in the liver, where insulin's inhibitory effect on PFK2 helps regulate glycolysis and gluconeogenesis. By decreasing PFK2 activity, insulin reduces the production of fructose-2,6-bisphosphate, an important allosteric activator of phosphofructokinase-1 (PFK1), which is a key regulatory enzyme in glycolysis. Some studies have investigated the role of other factors, such as metformin, in regulating PFK2 activity, but the most relevant study to this question is 1, which directly addresses the effect of insulin on PFK2 stimulation. Key points to consider include:

  • Insulin's effect on PFK2 stimulation is not mediated by changes in cAMP and effector levels or inhibition of cAMP-dependent protein kinase dissociation 1.
  • Insulin promotes the dephosphorylation of PFK2 through activation of protein phosphatases, leading to its inactivation 1.
  • The regulatory mechanism of PFK2 by insulin is important for fine-tuning carbohydrate metabolism based on the body's energy needs. Other studies, such as 2 and 3, have investigated the role of protein phosphatases in regulating insulin signaling, but they do not directly address the question of how insulin decreases PFK2 stimulation. Therefore, the most relevant and recent study to this question is 1, which provides evidence for the mechanism by which insulin decreases PFK2 stimulation.

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