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Table 1 The „IDE switch": a) surges (particularly those of a pathological nature) in the extracellular/blood level of insulin and b) defects in the activity of intracellular IDE are functionally equivalent to one another in that they both lead to an increase in intracellular insulin, the former through augmented insulin internalization [31] and the latter through decreased insulin degradation.

From: Intracellular insulin in human tumors: examples and implications

Extracellular/blood insulin Intracellular IDE activity Intracellular insulin Intracellular insulin-RB heterodimers Cell proliferation
Normal Normal Minimal Minimal Normal
Increased* Normal Increased Increased Increased
Normal/Increased* Defective Increased Increased Increased
  1. *i.e. hyperinsulinemia
  2. As a result, elevated intracellular insulin stimulates cell proliferation by binding and thereby inactivating the RB tumor suppressor, both in neoplastic diseases and in aging-related morbidities such as Syndrome X or, respectively, the metabolic syndrome which includes various clinical manifestations such as hyperinsulinemia, insulin resistance, obesity, type 2 diabetes and hypertension [32]. Interestingly, this model is supported by experimental data revealing increased intracellular insulin concentrations in monocytes from obese patients and obese diabetic patients vs. those from normal subjects [33].