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.
Service d'Endocrinologie, Nutrition, Maladies Métaboliques, Hôpital Sainte-Marguerite, Marseille, France.
M A
MA
Christofilis
M
M
Remacle-Bonnet
C
C
Atlan-Gepner
F
F
Garrouste
B
B
Vialettes
P
P
Fuentes
R
R
Guidicelli
G
G
Pommier
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