ROLE OF INSULIN-LIKE GROWTH-FACTOR-II AND IGF BINDING-PROTEINS IN EXTRAPANCREATIC TUMOR HYPOGLYCEMIA

Serum from patients with extrapancreatic tumor hypoglycemia (EPTH) contains elevated levels of big (pro) IGF II which disappears after successful removal of the tumor. Nevertheless, total IGF II serum levels are mostly found in the normal range both before and after operation. Why then do these patients become hypoglycemic? Oversecretion of big IGF II leads to suppression of growth hormone (GH). As a consequence, formation of a GH-dependent 150-kD IGF binding protein (BP) complex is impaired which normally carries 70-80% of total serum IGF II and largely restricts its bioavailability. Impaired formation of the 150-kD complex leads to a shift of IGF II to a 50-kD IGFBP complex, resulting in a 30-fold shorter serum half-life of IGF II, increased turnover and enhanced bioavailability. Insulin target organs are thus exposed to an enormous insulin-like potential which is continuously provided by oversecreted big IGF II and causes increased glucose consumption by skeletal muscle, inhibition of hepatic glucose production, inhibition of lipid mobilisation from adipose tissue, and pronounced hypoglycemia.