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Total and free IGF serum levels

It was one of the riddles of early insulin-like growth factor (IGF) research that the permanent insulin-like potential of circulating IGF by far exceeded that of fasting serum insulin levels without obvious effects on glucose homeostasis. The total serum level of IGF-I and -II in normal adults, but also in insulin-deficient diabetic patients, lies around 1 µg/ml, which corresponds to an insulin-like activity of 200–300 µU/ml of insulin equivalents (1). This insulin-like potential would be expected to cause permanent hypoglycemia and should prevent diabetes. The riddle was solved when highaffinity IGF-binding proteins (IGFBPs) which specifically bind IGFs and limit their bioavailability were discovered in serum. Circulating IGF is found in two major IGFBP complexes with molecular masses of 150 and 40–50 kDa. Approximately 80% of the total serum IGF is associated with the 150 kDa complex. It has a long serum half-life (12–16 h) due to restricted capillary permeability

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