DİYABETTE YENİ TERAPOTİK HEDEF BİYOBELİRTEÇ: İNSÜLİN BENZERİ BAĞLAYICI PROTEİNLER

Abstract

Diyabet giderek artan global bir sağlık sorunudur. Bu nedenle teşhis ve tedavi yöntemlerine alternatif, etkili, kolay kullanımlı terapötik biyobelirteç çalışmaları oldukça önemlidir. İnsülin benzeri büyüme faktörleri (IGF'lerin) potansiyel terapötik olarak değerlendirilmektedir. IGF ailesinin; diyabet, kanser, büyüme geriliği, kas-iskelet sistemi hastalıkları ve nörodejeneratif hastalıkların tedavisinde kullanım alanları mevcuttur. IGF’ler yapısal olarak insüline benzer ve biyolojik sıvıda, insülin benzeri bağlayıcı protein (IGFBP)’lere bağlanmış halde bulunur. Şu ana kadar karakterize edilmiş yedi memeli IGFBP’i bulunur.IGFBP’ler, IGF’lere Tip-1 IGF reseptörlerinden daha yüksek afinitede bağlanırlar. IGFBP-3 diğer IGFBP’ler ile sürekli ilişkisi olan bir proteindir. Karaciğer, adipositler, böbrekler ve bağırsaklar gb bir çok dokuda bulunur. IGF-1; IGFBP-3 ve ALS (acid labile subunit) ile birlikte yüksek moleküler kütleli üçlü bir kompleks halinde bulunur. IGFBP-3, diyabetik hastalarda glukoz homeastazında çok önemli rol oynamaktadır. Yapılan klinik çalışmalar, IGFBP-3'ün diyabette anahtar bir modülatör olabileceğini gösterir.

Keywords

• Diyabet;
• İnsülin benzeri büyüme faktörleri;
• insülin benzeri bağlayıcı protein-3

References

1. Ahmed, R.L., Thomas, W., Schmitz, K.H. (2007). Interactions between insulin, body fat, and insulin-like growth factor axis proteins. Cancer Epidemiology Biomarkers and Prevention, 16, 593-597.
2. Ahmed, S., Yamamoto, K., Sato, Y., Ogawa, T., Herrmann, A., Higashi, S., et al. (2003). Proteolytic processing of IGFBP-related protein-1 (TAF/angio- modulin/mac25) modulates its biological activity. Biochemical and Biophysical Research Communications, 310, 612-618.
3. Amoui, M., Craddock, B.P., Miller, W.T. (2001). Differential phosphorylation of IRS-1 by insulin and insulin-like growth factor I receptors in Chinese hamster ovary cells. Journal of Endocrinology, 171,153–162.
4. Bach, L.A., Hsieh, S., Sakano, K., Fujiwara, H., Perdue, J.F., Rechler, M.M. (1993). Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6. Journal of Biological Chemistry, 268, 9246-9254.
5. Baxter, R.C., Holman, S.R., Corbould, A. (1995).Regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia. Journal of Clininical Endocrinology Metabolism, 80, 2700–2708.
6. Baxter, R.C., Martin, J.L., Beniac, V.A. (1989). High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum. Journal of Biological Chemistry, 264, 11843-11848.
7. Bienvenu, G., Seurin, D., Le Bouc, Y., Even, P., Babajko, S., Magnan, C. (2005). Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain. Diabetologia ,48 ,1189e1197.
8. Blat, C., Villaudy, J., Binoux, M. (1994). In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. Journal of Clinical Invesigation, 93, 2286–2290. Böni-Schnetzler, M., Schmid, C., Mary, J.L., Zimmerli, B., Meier, P., Zapf, J., et al.(1990). Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes. Molecular Endocrinology, 4, 1320-1326

9. Boonen, S., Rosen, C., Bouillon, R. (2002). Muskuloskeletal effects of the recombinant human IGF-I/IGF binding protein-3 complex in osteoporotic patients with proximal femoral fracture, a double blind, placebo-controlled pilot study. The Journal of Clinical Endocrinology Metabolism, 87, 1593–1599.
10. Chahal, J., Chen, C.-C., Rane, M.J., Moore, J., Barati, M., Song, Y., et al. (2008). Regulation of insulin-response element binding protein-1 in obesity and diabetes, potential role in impaired insulin-induced gene transcription. Endocrinology, 149, 4829- 4836.
11. Clemmons, D.R. (2016). Role of IGF Binding Proteins in Regulating Metabolism. Trends in Endocrinology & Metabolism, 27, 375-391.
12. Clemmons, D.R., Moses, A.C., Mckay ,M.J., Sommer, A., Rosen, D.M., Ruckle, J. (2000). The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1Diabetes, Evidence for in Vivo Biological Activity. The Journal of Clinical Endocrinology Metabolism, 85, 1518-1524.
13. Daughaday, W.H., Kapadia, M. (1989). Significance of abnormal serum binding of insulin- like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors. Proceedings of the National Academy of Sciences, 86, 778–6782.
14. Davenport, M.L., Isley, W.L., Pucilowska, J.B. (1992). Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery. The Journal of Clinical Endocrinology Metabolism, 75, 590–595.
15. Daza, D.O., Sundstrom, G., Bergqvist, C.A., Duan, C., Larhammar, D. (2011). Evolution of the insulin-like growth factor binding protein (IGFBP) family. Endocrinology, 152, 2278–2289.
16. Durham, S.K., Mohan, S., Liu, F. (1997). Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum. Pediatric Research, 42, 335–341.
17. Firth, S.M., Baxter, R.C. (2002). Cellular actions of the insulin-like growth factor binding proteins. Endocrine Reviews, 23, 824–854.
18. Friedrich, N et al. (2014). Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays. The Journal of Clinical Endocrinology Metabolism, 99, 1675–1686.
19. Gederet ,Y.T., Öztürk, B., Karagözoğlu, E., Gök, M., Tiftik, A.M. (2004). Malign-Nonmalign plevral efüzyon ayırıcı tanısında IGF ve IGFBP’lerin rolü. Genel Tıp Dergisi, 14,139-143.
20. Gleason, C.E., Ning, Y., Cominski, T.P., Kaestner, K.H., Pintar, J.E., Birnbaum, M.J. (2010). Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth. Molecular Endocrinology, 24,178-192.
21. Gu, H.F., Gu, T., Hilding, A., Zhu, Z., Kärvestedt, L., Östenson, C., et al. (2013). Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes. Clinical Epigentics, 5, 1-7.
22. Gude, M.F., Frystyk, J., Flyvbjerg, A., Bruun, J.M., Richelsen, B., Pedersen, S.B. (2012). The production and regulation of IGF and IGFBPs in human adipose tissue cultures. Growth Hormone and IGF Research, 22, 200-205
23. Guler, H.P., Zapf, J., Schmid, C. (1989). Insulin-like growth factors I and II in healthy man, Estimations of half-lives and production rates. Acta Endocrinologica, 121, 53–758.
24. Harish, V. (2015). Theoretical and Computational Studies of Peptides and Receptors of the Insulin Family. Membranes, 5, 48-83.
25. Haywood, N.J., Slater, T.A., Matthews, C.J., B, Stephen, W.B. (2019). The insulin like growth factor and binding protein family, Novel therapeutic targets in obesity & diabetes. Molecular Metabolism, 19, 86-96.
26. Hawkes, C., ve Kar S. (2004). The insulin-like growth factor-II/mannose-6-phosphate receptor, structure, distribution and function in the central nervous system. Brain Research Reviews, 44, 117– 140.
27. Heald, A.H., Siddals, K.W., Fraser, W., Taylor, W., Kaushal, K., Morris, J., et al. (2002). Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macro- vascular disease and hypertension in type 2 diabetes. Diabetes, 51, 2629-2636.
28. Hjortebjerg, R., & Frystyk, J. (2013). Determination of IGFs and their binding proteins. Best Practice & Research Clinical Endocrinology & Metabolism, 27, 771–78.
29. Jones, J.I., & Clemmons, D.R. (1995) Insulin-like growth factors and their binding proteins, biological actions. Endocrine Research, 16, 3–34.
30. Lalou, C., Sawamura, S., Segovia, B., Ogawa, Y., Binoux, M. (1997). Proteolytic fragments of insulin-like growth factor binding protein-3, N-terminal sequences and relationships between structure and biological activity. Comptes Rendus de l’Academie Sciences III, 320, 621–628.
31. Lee, C.Y., & Rechler, M.M. (1995). A major portion of the 150-kilodalton insulin-like growth factor-binding protein (IGFBP) complex in adult rat serum contains unoccupied, proteolytically nicked IGFBP-3 that binds IGF-II preferentially. Endocrinology, 136, 668–678.
32. Lee, P.D., Giudice, L.C., Conover, C.A.P.D. (1997). Insulin-like growth factor binding protein-1, recent findings and new directions. Proceedings of the Society for Experimental Biology and Medicine, 216, 319-357.
33. LeRoith, D., Werner, H., Beitner-Johnson, D. (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrine Reviews, 16, 143-146.
34. Levetown, M. (2002). Modulation of types I and II acute phase reactants with insulin-like growth factor-I/binding protein 3 complex in severely burned children. Critical Care Medicine, 30, 255–257.
35. López-Bermejo, A., Khosravi, J., Fernández-Real, J.M., Hwa, V., Pratt, K.L., Casamitjana, R., et al. (2006). Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/ MAC25). Diabetes, 55, 2333- 2339.
36. Lu, S., Purohit, S., Sharma, A., et al. (2012). Serum insulin-like growth factor binding protein 6 (IGFBP6) is increased in patients with type 1 diabetes and its complications. International Journal of Clinical and Experimental Medicine, 5, 229-237.
37. Maridas, D.E., Demambro, V.E., Le, P.T., Mohan, S., Rosen, C.J. (2018). IGFBP4 is required for adipogenesis and influences the distribution of adipose depots. Endocrine Reviews, 158, 3488-3500.
38. Martin, J.L., & Baxter, R.C. (1986). Insulin-like growth factor-binding protein from human plasma, Purification and characterization. Journal of Biological Chemistry, 261, 8754–8760.
39. Mazerbourg, S., Callebaut, I., Zapf, J., Mohan, S., Overgaard, M., Monget, P. (2004). Up date on IGFBP-4, regulation of IGFBP-4 levels and functions, in vitro and in vivo. Growth Hormone and IGF Research, 14, 71-84.
40. Murphy, L.J., Molnar, P., Lu, X., Huang, H. (1995). Expression of human insulin-like growth factor-binding protein-3 in transgenic mice. Journal of Molecular Endocrinology. 15, 293–303.
41. Nedic, O., & Masnikosa, R. (2008). The change in the circulating insulin-like growth factor binding protein 1 isoform pattern during the course of oral glucose tolerance test. Metabolism 57,658-661.
42. Nissley, P., & Kiess, W. (1991). Reciprocal modulation of binding of lysosomal enzymes and insulin-like growth factor-II (IGF-II) to the mannose 6-phosphate/IGF-II receptor. Advances in Experimental Medicine and Biology, 293, 311-324.
43. Okajimina, T., Iwashita, M., Takeda, Y. (1993). Inhibitory effects insulin-like growth factor binding proteins 1 and 3 on IGF activated glucose consumption in mouse Balb/c3T3 fibroblasts. Journal of Endocrinology, 133, 457– 470.
44. Raipathak, S.N. (2012). Insulin-like growth factor axis and risk of type 2 diabetes in women. Diabetes, 61, 2248–2254
45. Ranke, MB. Emeritus. (2015). Insulin-like growth factor binding-protein-3 (IGFBP-3). Best Practice & Research Clinical Endocrinology & Metabolism, 29, 701-711.
46. Rechler, M.M. (1993). Insulin-like Growth Factor Binding Proteins. Vitamins & Hormones, 47, 1-114.
47. Rechler, M.M., & Clemmons, D.R. (1998). Regulatory Actions of Insulin-like Growth Factor-binding Proteins. Technology, Education, Management, Informatics Journal, 9, 176-183.
48. Rinderknecht, E., & Humbel, R.E. (1978a). Primary structure of human insulin-like growth factor II., FEBS Letters, 89, 283-286.
49. Rinderknecht, E., & Humbel, R.E. (1978b). The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. Journal of Biological Chemistry. 253, 2769-2776.
50. Rogol, A.D., Jacobson, W., Smith A. A. (2002). The double-blind, randomized, placebo-controlled, study to determine the döşe response profile of rhIGF-I/rhIGFBP-3 in subjects with Type 2 Diabetes Mellitus requiring insulin therapy. Poster American Diabetes Association. 61.
51. Salmon, W.D., & Daughaday W.H. (1957). A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. Journal of Laboratory and Clinical Medicine, 49, 825-836
52. Savage, M.O., Camacho-Hübner, C., Dunger, D.B. (2004). Therapeutic applications of the insulin-like growth factors. Growth Hormone & IGF Research, 14, 301–308.
53. Schneider, M.R., Wolf, E., Hoeflich, A., Lahm, H. (2002). IGF-binding protein- 5, flexible player in the IGF system and effector on its own. Journal of Endocrinology, 172, 423-440.
54. Shimasaki, S., & Ling , N., (1991). Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1,-2, -3, -4, -5 and -6). Progress in Growth Factor Research, 3, 243-266.
55. Thrailkill, K.M. (2000). Insulin-like growth factor-I in diabetes mellitus, its physiology, metabolic effects, and potential clinical utility. Diabetes Technology& Therapeutics, 2, 69–80.
56. Twigg, S.M., & Baxter, R.C. (1998). Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. Journal of Biological Chemistry, 273, 6074–6079.
57. Vivilan, H., Youngman, O.H., Rosenfeld, R.G. (1999). The Insulin-Like Growth Factor- Binding Protein(IGFBP) Superfamily. The Endocrine Society. 20, 761–787.
58. Wang, Y., Nishida, S., Sakata, T., Elalieh, H.Z., Chang, W., Halloran, B.P., Doty, S.B., Bikle, D.D. (2006). Insulin-Like Growth Factor-I Is Essential for Embryonic Bone Development. The Endocrine Society, 47, 4753–476.
59. Wheatcroft, S.B., Kearney, M.T., Shah, A.M., Ezzat, V.A., JR Miell, M., Modo, et al. (2007). IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes, 56, 285-294.
60. Wild, S., Roglic, G., Green, A., Sicree, R., King, H. 2004. Estimates for the year 2000 and projections for 2030. Diabetes Care, 27,1047-1053.
61. Wood, WI et al. (1988). Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. Molecular Endocrinology, 2, 1176–1185.
62. Yamada PM, Lee K. (2009). Perspectives in mammalian IGFBP-3 biology, local vs. systemic action. American Journal Physiology- Cell Physiology, 296, 954–976.
63. Yau, S.W., Harcourt, B.E. (2018). Serum IGFBP-2 levels are associated with reduced insulin sensitivity in obese children. Clinical Obesity, 8,184-190.
64. Zandbergen, A.A. (2006). The IGF-I system and the renal and hemodynamic effects of losartan in normotensive patients with type 2 diabetes mellitus, a randomized clinical trial. Clinical Endocrinology, 64, 203–208.
65. Zapf, J. (1995). Insulin like growth factor binding proteins and tumor hypoglycemia. Trends in Endocrinology and Metabolism, 6, 37–42.
66. Zhao, D., Shen, L., Wei, Y., Xie, J., Chen, S., Liang, Y., et al. (2017). Identification of candidate biomarkers for the prediction of gestational diabetes mellitus in the early stages of pregnancy using iTRAQ quantitative proteomics. Proteomics Clinical Applications, 7-8.