Skip to main content

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].