@Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence (Chow et al. 2019)

2022-05-02: reference:

@Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence (Chow et al. 2019) #

• Insulin Resistance reduces Hexokinase-2, impairing glycolysis. This hampers ubiquination and degredation of p35, favoring its cleavage to p25, which hyperactivates CDK5 and interferes with the GSK-3β-induced degadation of β-Catenin.

  • CDK5 contributes to neuronal cell death while β-Catenin enters the neuronal nucleus and re-activates the cell cycle machinery. able to successfully divide, the neuron instead enters a senescent-like state.
  • So, I guess Calpain must in a way work against whatever ubiquinates/degredates p35…

• While insulin is of short-term benefit to neurons, sustained systemic exposure can trigger neuronal insulin resistance (IR)11 and quadruple the risk of Alzheimer’s disease12. Indeed, systemic hyperinsulinemia causes tissue ‘desensitization’ to insulin13,

  • It seems proper hyperinsulinemia is more or less synonymous with insulin resistance, as obviously it isn’t doing its job if glucose is controlled/constant.
  • Insulin transgenic mice to have extra copies of the gene had 2-4x plasma insulin levels, normal weight, and normal fasting glucose, but an exaggerated insulin response to glucose. Reduced insulin receptor binding and correlated with hypertriglyceridemia. Insulin Resistance and Hyperinsulinemia
  • Transgenic mice: Delayed onset of Beta Cell insulin release in response to glucose.