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01-10-2013 | Original Article

Effect of obesity and glycemic control on serum lipocalins and insulin-like growth factor axis in type 2 diabetic patients

Authors: Hala O. El-Mesallamy, Nadia M. Hamdy, Al-aliaa M. Sallam

Published in: Acta Diabetologica | Issue 5/2013

Abstract

Obesity, insulin resistance (IR), and progressive decline in pancreatic β-cell function are major features of type 2 diabetes mellitus (T2DM). Altered adipokines contribute to obesity-induced IR. Hence understanding of adipokines’ relation to obesity and glycemic control could be useful to improve disease outcomes. We aimed at determination of serum retinol binding protein-4 (RBP-4), lipocalin-2 (LCN-2), insulin-like growth factor-I (IGF-I), and its binding protein-3 (IGFBP-3) levels in T2DM patients with the impact of obesity and glycemic control on them and their relation to β-cell function. Serum insulin, RBP-4, LCN-2, IGF-I, and IGFBP-3 estimated by ELISA were examined in 32 T2DM patients and age- and sex-matched 20 healthy controls. Significant elevation was observed in serum RBP-4 (P < 0.001), LCN-2 (P < 0.01), and IGF-I/IGFBP-3 molar ratio (P < 0.05) in T2DM patients in comparison with healthy controls. There was no significant difference in them between nonobese and obese diabetics. However, RBP-4 and IGF/IGFBP-3 molar ratio were higher in uncontrolled than in controlled diabetic patients at P < 0.001 and P < 0.01, respectively. Moreover, RBP-4, LCN-2, and IGF-I/IGFBP-3 molar ratio were negatively correlated with β-cell function. In conclusion, serum RBP-4 and IGF-I/IGFBP-3 molar ratio but not LCN-2 were prominently elevated with poor glycemic control rather than obesity in T2DM patients. Whereas, declining β-cell function is associated with elevation of serum RBP-4, LCN-2 as well as IGF-I/IGFBP-3 molar ratio.

IDF (2009) Diabetes atlas, 4th edn. International Diabetes Federation. Available at: www.diabetesatlas.org

Li L, Wang C, Bao Y, Wu H, Lu J, Xiang K et al (2009) Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance. J Diabetes 1:125–130PubMedCrossRef

Tschoner A, Sturm W, Engl J, Kaser S, Laimer M, Laimer E et al (2008) Retinol-binding Protein 4, visceral fat, and the metabolic syndrome: effects of weight loss. Obesity 16:2439–2444PubMedCrossRef

Law I, Xu A, Lam K, Berger T, Mak T, Vanhoutte P et al (2010) Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes 59:4872–4882CrossRef

Lee J, Im J, Park K, Lee H, Shim J, Lee D (2009) Retinol binding protein 4 and insulin resistance in apparently healthy elderly subjects. Clinica Chimica Acta 400:30–32CrossRef

Yang Q, Graham T, Mody N, Preitner F, Peroni O, Zabolotny J et al (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436:356–362PubMedCrossRef

Graham T, Yang Q, Bluher M, Hammarstedt A, Ciaraldi T, Henry R et al (2006) Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354:2552–2563PubMedCrossRef

Cho Y, Youn B, Lee H, Lee N, Min S, Kwak S et al (2006) Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes. Diabetes Care 29:2457–2461PubMedCrossRef

Janke J, Engeli S, Boschmann M, Adams F, Bohnke J, Luft F et al (2006) Retinol-binding protein 4 in human obesity. Diabetes 55:2805–2810PubMedCrossRef

10.

Yao-Borengasser A, Varma V, Bodles AM et al (2007) Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab 92:2590–2597PubMedCrossRef

11.

Promintzer M, Krebs M, Todoric J, Luger A, Bischof M, Nowotny P et al (2007) Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor. J Clin Endocrinol Metab 92:4306–4312PubMedCrossRef

12.

Flo T, Smith K, Sato S, Rodriguez D, Holmes M, Strong R et al (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432:917–921PubMedCrossRef

13.

Jayaraman A, Roberts K, Yoon J, Yarmush D, Duan X, Lee K et al (2005) Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1: a proteomic analysis. Biotechnol Bioeng 91:502–515PubMedCrossRef

14.

Fujino R, Tanaka K, Morimatsu M, Tamura K, Kogo H, Hara T (2006) Spermatogonial cell-mediated activation of an IkappaBzeta-independent NF-kappaB pathway in sertoli cells induces transcription of the lipocalin-2 gene. Mol Endocrinol 4:904–915

15.

Wang Y, Lam K, Kraegen E, Sweeney G, Zhang J, Tso A et al (2007) Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53:34–41PubMedCrossRef

16.

Panidis D, Tziomalos K, Koiou E, Kandaraki E, Tsourdi E, Delkos D et al (2010) The effects of obesity and polycystic ovary syndrome on serum lipocalin-2 levels: a cross-sectional study. Reprod Biol Endocrinol 8:151PubMedCrossRef

17.

Denley A, Cosgrove L, Booker G, Wallace J, Forbes B (2005) Molecular interactions of the IGF system. Cytokine Growth Factor Rev 16:421–439PubMedCrossRef

18.

Cleveland-Donovan K, Maile LA, Tsiaras WG, Tchkonia T, Kirkland JL, Boney CM (2010) IGF-I activation of the AKT pathway is impaired in visceral but not subcutaneous preadipocytes from obese subjects. Endocrinology 151(8):3752–3763PubMedCrossRef

19.

Jogie-Brahim S, Feldman D, Oh Y (2009) Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev 30(5):417–437PubMedCrossRef

20.

Rajpathak S, Gunter M, Wylie-Rosett J, Ho G, Kaplan R, Muzumdar R, Rohan T, Strickler H (2009) The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev 25:3–12PubMedCrossRef

21.

Lam C, Chen M, Lacey S, Yang Q, Sullivan L, Xanthakis V, Safa R, Smith H, Peng X, Sawyer D, Vasan R (2010) Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community. Arterioscler Thromb Vasc Biol 30(7):1479–1484PubMedCrossRef

22.

Rajpathak S, McGinn A, Strickler H, Rohan T, Pollak M, Cappola A et al (2008) Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults. Growth Horm IGF Res 18:166–173PubMedCrossRef

23.

Trinder P (1969) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24–27

24.

Abraham E, Huff T, Cope N, Wilson J, Bransome E, Huisman T (1978) Determination of the glycosylated hemoglobins (HbA1) with a new microcolumn procedure. Suitability of the technique for assessing the clinical management of diabetes mellitus. Diabetes 27:931–937PubMedCrossRef

25.

Henry RJ (1974) Clinical chemistry, principles and techniques, 2nd edn. Harper and Row, New York, p 525

26.

Siedel J, Hagele E, Ziegenhorn J, Wahlefeld A (1983) Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 29:1075–1080PubMed

27.

Richmond W (1973) Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 19(12):1350–1356PubMed

28.

Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11(6):583–595PubMed

29.

Bergmeyer HU (1985) Methods of enzymatic analysis, vol VIII, 3rd edn. VCH Verlagsgesellschaft, Weinheim, pp 154–160

30.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef

31.

Wolpin B, Michaud D, Giovannucci E, Schernhammer E, Stampfer M, Manson J, Cochrane B, Rohan T, Ma J, Pollak M, Fuchs C (2007) Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts. Br J Cancer 97:98–104PubMedCrossRef

32.

Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, Smith RJ, Smith SR (2011) Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Diabetes Care 34:1424–1430PubMedCrossRef

33.

Kanat M, Winnier D, Norton L, Arar N, Jenkinson C et al (2011) The relationship between β-cell function and glycated hemoglobin: results from the veterans administration genetic epidemiology study. Diabetes Care 34:1006–1010PubMedCrossRef

34.

Maedler K, Schulthess F, Bielman C, Berney T, Bonny C, Prentki M, Donath M, Roduit R (2008) Glucose and leptin induce apoptosis in human β-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases. FASEB J 22:1905–1913PubMedCrossRef

35.

Liu X, Hamnvik O, Petrou M, Gong H, Chamberland J et al (2011) Circulating lipocalin 2 is associated with body fat distribution at baseline but is not an independent predictor of insulin resistance: the prospective Cyprus metabolism study. Eur J Endocrinol 165:805–812PubMedCrossRef

36.

Thrailkill K, Moreau C, Cockrell G (2010) Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus. Endocrine 37(2):336–343PubMedCrossRef

37.

Bruun C, Heding PE, Ronn SG, Frobose H, Rhodes CJ, Mandrup-Poulsen T, Billestrup N (2009) Suppressor of cytokine signalling-3 inhibits tumor necrosis factor-alpha induced apoptosis and signalling in beta cells. Mol Cell Endocrinol 311(1–2):32–38PubMedCrossRef

38.

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

Title: Effect of obesity and glycemic control on serum lipocalins and insulin-like growth factor axis in type 2 diabetic patients
Authors: Hala O. El-Mesallamy
Nadia M. Hamdy
Al-aliaa M. Sallam
Publication date: 01-10-2013
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 5/2013
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-012-0373-6

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