Alleviation of non-islet cell tumour hypoglycaemia by growth hormone therapy is associated with changes in IGF binding protein-3.
The hypoglycaemia caused by non-islet cell tumours is often associated with an increase in plasma insulin-like activity. In many cases there is a relative if not always absolute increase in plasma insulin-like growth factor II (IGF-II). Growth hormone (GH) secretion is almost invariably depressed as is the plasma insulin response to oral glucose. Despite the high concentration of IGFs (i.e. IGF-I and IGF-II) normally found in the plasma of healthy people their potential hypoglycaemic effect is not manifest due to the tightness with which they are bound to specific binding proteins (IGFBPs). Plasma levels of the major binding protein (IGFBP-3), which is GH-dependent, were depressed in three patients with tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to levels which were approximately equimolar to total plasma IGF concentrations, alleviated the hypoglycaemia and restored the plasma insulin responses to oral glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated IGFBP-3 in association with a pre-existing acid-labile subunit to form high molecular weight complexes which prevent IGF-II gaining access to tissues receptors through which it exerts its hypoglycaemic effects.
Teale
J D
JD
Department of Clinical Biochemistry, St Luke's Hospital, Guildford, Surrey, UK.
Blum
W F
WF
Marks
V
V
D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy*; D018969:Insulin-Like Growth Factor Binding Proteins; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D013006:Growth Hormone