Title: Study of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-1 Relation to Insulin Resistance in Normal Persons and Type 2 Diabetics

Authors: Khalifa A.M., Ismael A.A.,El Neily D.A., Abd El Ghafour R.A.

 DOI:  http://dx.doi.org/10.18535/jmscr/v3i11.03

Abstract

Aim and Background: IGF binding proteins predominantly control the access of IGFs to tissues and cell-surface IGF receptors. Of these, IGFBP-1 is the most likely candidate for acute regulation of IGF actions because of its acute down regulation by insulin and upregulation by other glucoregulatory hormones and cytokines and in catabolic states. This study was undertaken to to assess the relation of the IGF-1 and IGFBP-1 to insulin resistance in a group of adult Egyptian diabetics and non diabetic population.

Subjects and Methods:This study was conducted on 45 adult males with age between 20-50 years. They were divided into group I (n=25) type 2 diabetics and group II (n=20) non diabetics.  Patient`s general information was noted, anthropometrical measurements were conducted and The eligible participants were asked to overnight fast for 8 hours. Blood was sampled for FBG, fasting Insulin, fasting IGF1, fasting IGFBP-1 And IR (HOMA-IR) was analyzed. Insulin and IGF-1 were analyzed by chemiluminescent immunoassay, FBG was analyzed by the glucoseoxidase (enzymatic oxidation) method and IGFBP-1 was analyzed by IGFBP-1 ElLISA

Results: Diabetic group had IGF1(P=0.0001) and  IGFBP-1(P=0.041)values statistically lower than non diabetic group. Diabetic group had a significant negative correlation between levels of FBG and those of IGF-1(p=0001).We noted that, diabetic group had a significant negative correlation between IGF-1 and IR(HOMA-IR) (p=.045) and a significant negative correlation between IGFBP1 and IR(HOMA-IR) (p=.046).

Conclusion: IGF1 and IGFBP-1 seems to be at lower levels in Type 2diabetics than in normal subjects, IGF1 seems to be negatively associated with fasting glucose inType 2diabetics and Insulin resistance (HOMA-IR) seems to be negatively associated with IGF1 and IGFBP-1 in Type 2 diabetics.

Keywords: IGFBP-1, IGF-1, IR(HOMA-IR), Type 2 diabetics

References

1.      Daughaday WH, Rotwein P. Insulin-like growth factors I and II: peptide,messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989; 10:68–91.

2.      R.S. Sherwin, K. Greenawalt, G.I. Shulman Simultaneous in-sulin-like growth factor I and insulin resistance in obese zucker rats. Diabetes, 1992;41: 691–697.

3.      S.Y. Nam, E.J. Lee, K.R. Kim .Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone .Int J Obes Relat Metab Disord,1997;21:355–359.

4.      Ritvos O, Ranta T, Jalkanen J, Suikkari A-M, et al. Insulin-like growth factor (IGF) binding protein from human deciduas inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology 1988; 122:2150–7.

5.      Holly JMP. The physiological role of IGFBP-1. Acta Endocrinol (Copenh) 1991;124: 55–62.

6.      Westwood M, Gibson JM, Williams AC, et al. Hormonal regulation of circulating insulin-like growth factor binding protein-1 phosphorylation status. J Clin Endocrinol Metab 1995; 85: 3520 –7.

7.      Yki-Jarvinen, H. et al.  Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo. J. Clin. Endocrinol. Metab. 1995;80: 3227–3232.

8.      K. Brismar, E. Fernqvist Forbes, J. Wahren, K. Hall 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 Endocrinol Metab,1994; 79: 872–878.

9.      J. Frystyk, E. Vestbo, C. SkjÒrbÒk, C.E. Mogensen, H. Èrskov .Free insulin-like growth factors in human obesity .Metabolism, 1995;44 (Suppl 4) :37–44

10.  Kaushal, K. et al.The impact of abnormalities in IGF and inflammatory systems on the metabolic syndrome. Diabetes Care2004; 27:2682–2688.

11.  Travers, S.H. et al.Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children. J. Clin. Endocrinol. Metab.1998; 83:1935–1939.

12.  Maddux, B.A. et al.IGF-binding protein-1 levels are related to insulin-mediated glucose disposal and are a potential serum marker of insulin resistance. Diabetes Care 2006; 29: 1535–1537.

13.  Rajpathak, S.N. et al. Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults. Growth Horm. IGF Res. 2008;18: 166–173.

14.  Heald, A.H. et al. Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations. Diabetologia 2001; 44:333–339.

15.  Lewitt, M.S. et al.Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men. Diabetologia 2008; 51:1135–1145.

16.  Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 2009;30:152–177.

17.  RH IGF-I in NIDDM Study Group. Evidence from a dose ranging study that recombinant insulin-like growth factor-I effectively and safely improves glycaemic control in non-insulin dependent diabetes mellitus. Diabetes 1996; 45 (suppl): 27A.

18.  Crowne EC, Samra JS, Cheetham T et al. The role of IGF-binding proteins in mediating the effects of recombinant human IGF-I on insulin requirements in type 1 diabetes mellitus. J Clin Endocrinol Metab 2001; 86: 3686–91.

19.  Poulos JE, Leggett Frazier N, Khazanie P et al. Circulating insulin-like growth factor I concentrations in clinically severe obese patients with and without NIDDM in response to weight loss. Horm Metab Res 1994; 26: 478-480.

20.  Srinivas, Anoop et al. Association between Serum IGF-1 and diabetes among U.S. adults. Diabetes care 2010;33: 2257–2259.

21.  Sandhu, M.S. et al. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet 2002; 359: 1740–1745.

22.  Xu J, Ji S, Venable DY, Franklin JL, Messina JL. Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. J Endocrinol 2005;184:481–492.

23.  Sandhu MS, Gibson JM, Heald AH et al.Association between insulin-like growth factor-I: insulin-like growth factor-binding protein-1 ratio and metabolic and anthropometric factors in men and women. Cancer Epidemiol Biomarkers Prev 2004; 13:166–170

24.  Golam Kabir , Mosaraf Hossain et al .Association of serum free IGF-1 and IGFBP-1 with insulin sensitivity in impaired glucose tolerance (IGT) International Journal of Diabetes Mellitus 2010;2: 144–147.

25.  Golam Kabir, MPhil Omar Faruque,  Mohammad Alauddin  et al. Association of serum free IGF-1 and IGFBP-1 with insulin sensitivity and insulin secretory defects in Bangladeshi type 2 diabetes mellitus. Journal of  Taibah University Medical Sciences 2014; 9(2): 132–138

26.  Swapnil N. et al .Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women.DIABETES 2012; 61 ; 2248-2254.

27.  Federici M, Porzio O, Zucaro L et al. Increased abundance of insulin/IGF-I hybrid receptors in adipose tissue from NIDDM patients. Mol Cell Endocrinol 1997;135:41–47.

28.  Modan-Moses D, Janicot M, McLenithan JCet al. Expression and function of insulin/insulin-like growth factor I hybrid receptors during differentiation of 3T3-L1 preadipocytes. Biochem J 1998; 333:825–831.

29.  Kawai M, Rosen CJ. The IGF-I regulatory system and its impact on skeletal and energy homeostasis. J Cell Biochem 2010; 111:14–19.

30.  Lyssenko V, Almgren P, Anevski D et al.Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes2005; 54:166–174.

31.  Kuppan GokulakrishnanKaliyaperumal et alCirculating levels of insulin-like growth factor binding protein–1 in relation to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai Urban Rural Epidemiology Study).Metabolism 2012; 61(1)43–46.

32.  Liew CF, Wise SD, Yeo KP et al.Insulin-like growth factor binding protein-1 is independently affected by ethnicity, insulin sensitivity, and leptin in healthy, glucose-tolerant young men. J Clin Endocrinol Metab 2005; 90:1483–1488.

33.  Clauson PG,Brismar K, Hall K Insulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden. Scand J Clin Lab Invest. 1998 Jul; 58(4):353-60.

34.  Rajpathak SN, Gunter MJ, Wylie-Rosett J, et al. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev 2009; 25:3–12.

35.  Williams T, Berelowitz M, Joffe SN, et al. Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 1984;311:1403–1407.

36.  Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995;16:3–34.

37.  Wabitsch M, Heinze E, Debatin KM, Blum WF. IGF-I- and IGFBP-3-expression in cultured human preadipocytes and adipocytes. Horm Metab Res 2000;32: 555–559.

38.  Böni-Schnetzler M, Schmid C, Mary JL, et al. Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes. Mol Endocrinol 1990;4:1320–1326.

39.  Brismar K, Fernqvist-Forbes E, Wahren J, Hall K. 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 Endocrinol Metab 1994; 79: 872–878.

40. FrystykJ, SkjaerbaekC, VestboE, et al. Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes. Diabetes Metab Res Rev 1999; 15: 314–322.

Corresponding Author

Reem Ahmed Mohammed Abd El Ghafour (Abd El Ghafour R.A.)

Specialist of Internal Medicine, Damanhour Medical Institute, Egypt

Email: This email address is being protected from spambots. You need JavaScript enabled to view it., phone: 002 01227943121