Association between the Pattern of IGFBP-1 Alteration and the Glucose/Insulin Metabolic Control

Abstract

Little is known on the possible association between impaired glucose/insulin metabolism, the pattern of IGFBP-1 phosphorylation and the complex formation with other serum proteins. In this study, the concentration, isoform, multimer and complex pattern of IGFBP-1 was compared in healthy persons and patients with type 2 diabetes mellitus or with hypoglycemia. Concentrations of insulin and IGFBP-1 were determined by radioimmunoassay. Metal affinity and immunoaffinity chromatography were used for the separation of molecular forms of IGFBP-1, which were detected by immunoblotting and SELDI. The counter directional change in insulin and IGFBP-1 concentrations, expressed as a factor that takes into consideration the rate of insulin increase and IGFBP-1 decrease after glucose intake was approximately twice more pronounced in patients with diabetes than in healthy and hypoglycemic persons. The alteration in the phosphorylation pattern of IGFBP-1 due to diabetes or hypoglycemia was not observed. IGFBP-1 multimers found in the circulation of patients with diabetes type 2 differed from those detected in the circulation of others: there were 3 molecular forms between 90 and 100 kDa (compared to one in patients with hypoglycemia or 2 in healthy persons), 2 of which were α₂M-reactive and one not. These results suggest a possible greater involvement of IGF system in glucose regulation in patients with diabetes type 2.

Key words

IGFBP-1 - multimers - impaired glucose metabolism

• 1 Allen NE, Appleby PN, Davey GK. et al . The association of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians and vegans.  Cancer Epidemiol Biomarkers Prev. 2002;  11 1441-1448
• 2 Barnard RJ, Aronson WJ. Preclinical models relevant to diet, exercise, and cancer risk.  Recent Results Cancer Res. 2005;  166 47-61
• 3 Brismar K, Gutniak M, Póvoa G. et al . Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus.  J Endocrinol Invest. 1988;  11 599-602
• 4 Brismar K, Fernqvist-Forbes E, Wahren J. et al . Effect of insulin on the hepatic production of insulin-like growth factor binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.  J Clin Endicrinol Metab. 1994;  79 872-878
• 5 Colman PG, Thomas DW, Zimmet PZ. et al . New classification and criteria for diagnosis of diabetes mellitus.  Med J Aust. 1999;  170 375-378
• 6 Frystyk J, Grøfte T, Skjærbæk C. et al . The effect of oral glucose on serum free insulin-like growth factor-I and -II in healthy adults.  J Clin Endocrinol Metab. 1997;  82 3124-3127
• 7 Heald AH, Siddals KW, Fraser W. et al . Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes.  Diabetes. 2002;  51 2629-2636
• 8 Heald AH, Cade JE, Cruickshank JK. et al . The influence of dietary intake on the insulin-like growth factor (IGF) system across 3 ethnic groups: a population based study.  Public Health Nutr. 2003;  6 175-180
• 9 Lavoi J-M, Fillion Y, Couturier K. et al . Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1.  J Appl Physiol. 2002;  93 798-804
• 10 Lewitt MS, Saunders H, Baxter RC. Regulation of rat insulin-like growth factor binding protein-1: the effect of insulin-induced hypoglycemia.  Endocrinology. 1992;  131 2357-2364
• 11 Lewitt MS, Hall K, Bang P. et al . Altered response of insulin-like growth factor-binding protein 1 to nutritional deprivation in type 2 diabetes mellitus.  Metab Clin Exp. 2005;  54 275-280
• 12 Machida M, Kosako H, Shirakabe K. et al . Purification of phosphoproteins by immobilized metal affinity chromatography and its application to phosphoproteome analysis.  FEBS J. 2007;  274 1576-1587
• 13 Martinez de Icaya PM, Fernández C, Vázquez C. et al . IGF-I and its binding proteins IGFBP-1 and 3 as nutritional markers in prepubertal children.  Ann Nutr Matab. 2000;  44 139-143
• 14 Masnikosa R, živković B, Nedić O. IGFBP-1 forms associated with placental cell membranes.  J Serb Chem Soc. 2009;  74 707-716
• 15 Masnikosa R, Baričević I, Lagundžin D. et al . Characterisation of N-glycans bound to IGFBP-3 in sera from healthy adults.  Biochimie. 2010;  92 97-101
• 16 Matsukawa T, Inoue Y, Oishi Y. et al . Up-regulation of upstream stimulatory factors by protein malnutrition and its possible role in regulation of the IGF-binding protein-1 gene.  Endocrinology. 2001;  142 4643-4651
• 17 Mohamed-Ali V, Pinkney J. Therapeutic potential of insulin-like growth factor-1 in patients with diabetes mellitus.  Treat Endocrinol. 2002;  1 399-410
• 18 Motaghedi R, Gujral S, Sinha S. et al . Insulin-like growth factor binding protein-1 to screen for insulin resistance in children.  Diabetes Technol Ther. 2007;  9 43-51
• 19 Nedić O, Masnikosa R. The change in the circulating IGFBP-1 isoform pattern during the course of oral glucose tolerance test.  Metab Clin Exp. 2008;  57 658-661
• 20 Nedić O, Masnikosa R. Isolated receptors exhibit altered insulin/IGF interaction compared to membrane bound.  Biochemistry (Moscow). 2009a;  74 29-35
• 21 Nedić O, Masnikosa R. Separation of the molecular forms of the insulin-like growth factor (IGF)-binding proteins by affinity chromatography.  J Chromatogr. 2009b;  877 743-746
• 22 Rajpathak SN, McGinn AP, Strickler HD. et al . Insulin-like growth factor (IGF) axis, inflammation, and glucose intolerance among older adults.  Growth Horm IGF Res. 2008;  18 166-173
• 23 Sakai K, D’Ercole AJ, Murphy LJ. et al . Physiological differences in insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation in IGFBP-1 transgenic mice.  Diabetes. 2001a;  50 32-38
• 24 Sakai K, Busby WH, Clarke JB. et al . Tissue transglutaminase facilitates the polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) and leads to loss of IGFBP-1's ability to inhibit insulin-like growth factor-I-stimulated protein synthesis.  J Biol Chem. 2001b;  276 8740-8745
• 25 Vrieling A, Voskuil DW, Mesquita HBBD. et al . Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1, 2 and 3 in women in the Netherlands.  Cancer Causes Control. 2004;  15 787-796
• 26 Westwood M, Gibson JM, Davis AJ. et al . The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy.  J Clin Endocrinol Metab. 1994;  79 1735-1741
• 27 Westwood M, Gibson JM, White A. Purification and characterization of insulin-like growth factor-binding protein-1 phosphoform found in normal plasma.  Endocrinology. 1997;  138 1130-1136
• 28 Westwood M, Aplin JD, Collinge IA. et al . α₂-Macroglobulin: a new component in the insulin-like growth factor/insulin-like growth factor binding protein-1 axis.  J Biol Chem. 2001;  276 41668-41674
• 29 Wolk K, Larsson SC, Vessby B. et al . Metabolic, anthropometric, and nutritional factors as predictors of circulating insulin-like growth factor binding protein-1 levels in middle aged and elderly men.  J Clin Endocrinol Metab. 2004;  89 1879-1884
• 30 Zhang F, Sjöholm Å, Zhang Q. Attenuation of insulin secretion by insulin-like growth factor binding protein-1 in pancreatic β-cells.  Biochem Biophys Res Commun. 2007;  362 152-157

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