ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 P135

Characterisation of IGFBP1 molecular forms in healthy persons and patients with diabetes mellitus type 2 or hypoglycemia

Dragana Lagundzin & Olgica Nedic

Institute for the Application of Nuclear Energy-INEP, 11080 Belgrade, Serbia.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are involved in the regulation of glucose metabolism and metabolic disorders. IGFBP1 is the only IGF-binding protein that shows diurnal variation and is inversely correlated to the insulin level. IGFBP1 exists as non-phosphorylated protein and several phosphoforms. Phosphorylation affects the affinity of IGFBP1 for IGFs and, therefore, the ability to regulate IGF action. In the circulation IGFBP1 is associated with α2-macroglobulin (α2M) in a complex that may have an important role in controlling IGF action by regulating the amount of free IGFBP1. IGFBP1 was found to form multimers as well, which have low affinity for IGFs. The aim of this work was to investigate the kinetics of the alteration of IGFBP1 concentration during OGTT, together with the molecular distribution of IGFBP1, in healthy persons, patients with diabetes mellitus type 2 (DM2) or hypoglycemia (HG). It was found that IGFBP1 concentration significantly decreased 2 h after glucose intake in healthy and hypoglycemic persons, whereas in patients with diabetes a reduction in IGFBP1 became significant already after the first hour. The pattern of IGFBP1 phosphorylation and oligomerisation has been investigated using immunoaffinity chromatography with immobilised anti-α2M antibodies, SDS-PAGE and SELDI techniques. The relative ratio of IGFBP1 isoforms seemed the same in all three study groups, but the groups differed in respect to oligomer formation (90–100 kDa). There were three oligomeric forms detected in the circulation of DM2 patients, compared to one in HG patients and two in healthy persons. Oligomers had characteristic masses in samples from three study groups. These results suggest a possible greater involvement of IGF system in glucose/insulin metabolism in patients with diabetes mellitus type 2, than in healthy persons and patients with hypoglycemia.

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