Serum high molecular weight form of insulin-like growth factor II from patients with non-islet cell tumor hypoglycemia is O-glycosylated.
Non-islet cell tumor hypoglycemia (NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumors is thought to be a hypoglycemic agent. In patients with NICTH, the major form of IGF-II is high molecular weight form of IGF-II, designated as big IGF-II. The generation of big IGF-II in the NICTH syndrome is unclear. It has been reported that in the patients with NICTH big IGF-II lacks normal E-domain O-linked glycosylation, suggesting that the patient's big IGF-II might be generated by abnormal processing of pro-IGF-II. However, we have found that the apparent size of big IGF-II varies in sera from the patients with NICTH, and that there is a possibility that slower migration pattern of IGF-II might be because of a different size of sugar moiety attached to pro-IGF-II. In the present study using the sera from 10 patients with NICTH, we investigated the effect of O-glycosidase digestion on migration of IGF-II and analyzed the results by Western immunoblot. By Western immunoblot analysis the big IGF-II was reduced in size to 9.5 kDa in the enzyme-treated sera of the 10 patients with NICTH. The migration pattern is similar to that observed in sera of normal subjects after O-glycosidase digestion. These data indicate that big IGF-II from patients with NICTH is O-glycosylated, and the sizes of the sugar moiety are larger than those from normal subjects suggesting abnormal glycosylation in NICTH.
Hizuka
N
N
Department of Medicine II, Tokyo Women's Medical University, Japan. naomi-hi@hi-ho.ne.jp
Fukuda
I
I
Takano
K
K
Asakawa-Yasumoto
K
K
Okubo
Y
Y
Demura
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015153:Blotting, Western; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009369:Neoplasms / Q000150:complications*; D009439:Neuraminidase / Q000378:metabolism
D007335:Insulin-Like Growth Factor II; D006026:Glycoside Hydrolases; D009439:Neuraminidase