Gene expression and serum levels of insulin-like growth factors (IGFs) and IGF-binding proteins in a case of non-islet cell tumour hypoglycaemia

Growth Horm IGF Res. 1998 Dec;8(6):447-54. doi: 10.1016/s1096-6374(98)80297-9.

Abstract

We describe a case of non-islet cell tumour hypoglycaemia (NICTH) associated with a renal cell carcinoma. Serum insulin-like growth factors (IGFs) (including IGF-II E peptide), IGF-binding proteins (IGFBPs), insulin and C-peptide were measured before and after surgical removal of the tumour. IGFBPs were visualized by Western ligand blotting. Preoperatively 'big' IGF-II and IGFBP-2 levels were raised. IGF-I, IGFBP-1 and IGFBP-3 were low, while insulin, C-peptide and GH were undetectable. These changes were reversed by 2 days postoperatively. Protease assays showed little IGFBP-3 protease activity preoperatively. Preoperatively, neutral chromatography demonstrated most of the immunoassayable IGFBP-3 in a high molecular weight form with a small amount of IGF-II. Most of the IGF-II and big IGF-II eluted in lower molecular weight forms. Postoperative samples showed a shift in IGF-II which became increasingly associated with IGFBP-3 in both low and high molecular weight complexes. By Northern blotting, expression of all species of IGF-II mRNA in the tumour was 10-fold greater than in normal human liver. The tumour did not express IGFBP-1 or IGFBP-2. IGFBP-3 was expressed in small amounts, while the expression of IGFBP-4 was two-fold higher than in liver. In conclusion, we have confirmed high levels of big IGF-II and IGFBP-2 in NICTH, changes which are reversed postoperatively. The IGF-II is derived from the tumour which overexpresses these genes but IGFBP-2 probably arises from extratumour upregulation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blotting, Northern
  • C-Peptide / blood*
  • Carcinoma, Renal Cell / blood*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemia / etiology*
  • Insulin / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 1 / genetics
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Insulin-Like Growth Factor Binding Protein 2 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Proteins / blood*
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / analysis
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Kidney Neoplasms / blood*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / surgery
  • RNA, Messenger / genetics

Substances

  • C-Peptide
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II