Insulin Receptor

2022-04-12: reference:

Insulin Receptor #

Its ‘substrates’ are ligands that mediate its effects: IRS-1, IRS-2, 3P and 4P. After binding, PI3K is activated and AKT activates SNARE proteins by means of AS160, triggering translocation of GLUT4 vesicles from an internalized state to be merged into the membrane, whereby glucose can enter.

• β-Cell Hyperplasia Induced by Hepatic Insulin Resistance: Role of a Liver-Pancreas Endocrine Axis Through Insulin Receptor A Isoform
  • Liver IR knockout mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased Beta Cell mass, the extent of which was proportional to the deletion of hepatic IR. Eventually they failed to keep up.

Brain #

• Insulin in Central Nervous System: More than Just a Peripheral Hormone
  • Brain IR subunits differ from peripheral ones by the slightly lower molecular weight and by the absence of downregulation after exposure to high insulin levels
• Insulin and insulin-like growth factor receptors in the nervous system
  • Insulin is capable of down-regulating glial cell insulin receptors, but it has no such effect on neuronal cell receptors. Physiologically Unique Insulin Receptors on Neuronal Cells (Raizada et al. 1987))
  • Insulin receptors in rat brain cortex. Kinetic evidence for a receptor subtype in the central nervous system (Gammeltoft et al. 198)
    • IGF-I showed only 22% of the affinity for the type II receptor as did IGF-II, whereas IGF-II showed 45% of the affinity for type I receptors as did IGF-I.
    • “Negative cooperativity,” the mechanism by which the binding of insulin to its receptor progressively lowers the affinity of insulin receptors, was found to be absent in rat brain insulin receptors.
  • Identification and characterization of insulin receptors on foetal-mouse brain-cortical cells. (Van Schravendijk et al. 1984)
    • Mouse in vitro: high ambient insulin concentration actually increased insulin receptor number
• Physiologically Unique Insulin Receptors on Neuronal Cells
  • The observations suggest that the neuronal insulin receptor is physiologically and biochemically distinct from the peripheral non-neuronal and glial insulin receptors.
  • Insulin inhibited Norepinephrine uptake and stimulated Serotonin uptake.
  • studies have shown that astrocytic glial cells in primary culture from neonatal rat brain possess specific insulin receptors which are kinetically, physiologically and biochemically indistinguishable from the insulin receptors on peripheral target tissue (10,11)