Abnormal serum IGF-II transport in non-islet cell tumor hypoglycemia results from abnormalities of both IGF binding protein-3 and acid labile subunit and leads to elevation of serum free IGF-II

Autor: Bakula Trivedi, Robert C. Baxter, William H. Daughaday
Rok vydání: 1995
Předmět:
Zdroj: Endocrine. 3:425-428
ISSN: 1559-0100
0969-711X
DOI: 10.1007/bf02935648
Popis: The syndrome of non-islet cell tumor hypoglycemia (NICTH) is the result of hypersecretion of IGF-II by a tumor although serum IGF-II is seldom elevated. This is attributable to abnormalities of the IGF binding proteins (IGFBPs) present in NICTH which is characterized by a marked decrease in the fraction of IGFBP-3 present in the 150 kD complex with acid labile subunit (ALS) and a 2- to 4-fold increase in IGFBP-2. We studied the impact of these changes in IGFBPs on the concentration of free IGF-II using a neutral C-18 Sep-Pak extraction procedure. We found that free IGF-II was increased 8- to 20-fold in NICTH. Thus there is no limitation of free IGF-II for complex formation. Additional experiments were conducted to determfine whether ALS deficiency limits 150 kD complex formation. We observed that addition of purified ALS to NICTH sera only partially succeeded in converting smaller complexes containing IGFBP-3 to large 150 kD complexes. We conclude that both a functional deficiency of ALS and IGFBP-3 are present in NICTH sera. The increased free IGF-II in NICTH sera contributes greatly to bioactivity and largely explains the marked hypoglycemia of NICTH patients even when total serum IGF-II concentrations may remain within normal limits.
Databáze: OpenAIRE
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