Study of serum big-insulin-like growth factor (IGF)-II and IGF binding proteins in two patients with extrapancreatic tumor hypoglycemia, using a combination of Western blotting methods.
Extrapancreatic tumor hypoglycemia (EPTH) is associated with increased amounts of high-molecular-weight precursor forms of insulin-like growth factor (IGF)-II ('big-IGF-II') that have a primary role in the pathophysiology of hypoglycemia. In the present study, using Western ligand and immunoblotting methods, we investigated IGF-binding proteins (IGFBPs), IGFBP-3 proteolysis and big-IGF-II in pre- and postoperative serum from two patients with EPTH due to benign pleural fibroma. In the preoperative serum, IGFBP-3 was reduced and IGFBP-2 was increased compared with that from an age-matched healthy control. IGFBP-3 proteolysis was dramatically reduced in one patient, whereas no major alteration was observed in the other (9% and 120% of control serum, respectively). IGFBPs progressively returned to a subnormal pattern in postoperative serum, whereas IGFBP- 3 proteolysis remained greater than in preoperative serum in both patients at days 14 and 90 after surgery. High-molecular-weight forms of IGF-II predominate in EPTH serum (65% and 57% of total IGF-II immunoreactivity in patients 1 and 2, respectively, compared with 2 5% in control serum). Two forms, of molecular mass 10 and 12 kDa ('standard big-IGF-II') were present in both EPTH and control sera, whereas two additional forms, of molecular mass 15 and 18 kDa ('big big-IGF-II') were observed in EPTH sera only. Big big-IGF-II represented 72% and 55% of total high-molecular-weight forms of IGF-II in the two EPTH sera, respectively. All big forms of IGF-II disappeared from the serum as early as 6 h after surgery. This study shows that combination of simple Western blotting methods, available routinely in most laboratories, should prove useful in providing reliable physiopathological information in EPTH.
Christofilis
M A
MA
Service d'Endocrinologie, Nutrition, Maladies Métaboliques, Hôpital Sainte-Marguerite, Marseille, France.
Remacle-Bonnet
M
M
Atlan-Gepner
C
C
Garrouste
F
F
Vialettes
B
B
Fuentes
P
P
Guidicelli
R
R
Pommier
G
G
D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005350:Fibroma / Q000097:blood / Q000150:complications*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000097:blood / Q000150:complications*; D011498:Protein Precursors / Q000378:metabolism*
D018969:Insulin-Like Growth Factor Binding Proteins; D011498:Protein Precursors; C066038:proinsulin-like growth factor II; D007335:Insulin-Like Growth Factor II