Author(s): Malgorzata Malodobra-Mazur, Dorota Bednarska-Chabowska, Robert Olewinski, Zygmunt Chmielecki, Rajmund Adamiec, Tadeusz Dobosz
Aims/Introduction: The RBP4 level has been found to correlate positively with risk of insulin resistance and type 2 diabetes. However, the exact mechanism linking RBP4 with metabolic disorders is not clear. In presented study the associations of two single nucleotide polymorphisms located in promoter region of the RBP4 gene rs3758538 (-1265A>C) and rs3758539 (-803 G>A) with insulin resistance risk, RBP4 mRNA level and biochemical parameters were analyzed. Material and methods: Two polymorphisms were genotyped by multiplex minisequencing with the use of ABI PRISMÂ® SNaPshot Multiplex Kit. RBP4 gene expression analysis was done by Relative Real-Time PCR and normalized to Î²-actin and GUS-Î² genes. Insulin and cytokines were measured using commercial ELISA kits. Results: IR patients were characterized by increased RBP4 mRNA level in adipose tissue comparing to IS patients and control subjects, what correlated positively with insulin resistance. Polymorphism rs3758539 showed no differences in genotype frequencies between tested groups. The rs3758538 displayed higher number of C allele within type 2 diabetes patients. There was no relationship between genotype and RBP4 gene expression level. Furthermore, no relationship of investigated SNPs with insulin resistant phenotype has been noticed. Conclusions: Present results link the RBP4 gene expression level with insulin resistance pathogenesis. However, there is lack of association between analyzed SNPs with insulin resistant phenotype, RBP4 gene expression level and inflammatory state.
RBP4, Insulin resistance, SNP
- Karelis AD, St-Pierre DH, Conus F et al. Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab 2004; 89: 2569-2575
- Eckel RH, Alberti KG, Grundy SM et al. The metabolic syndrome. Lancet 2005; 365: 1415-1428
- Preis SR, Massaro JM, Robins SJ et al. Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham heart study. Nature 2010; 18: 2191-2198
- Alvehus M, BurÃ©n J, SjÃ¶strÃ¶m M et al. The human visceral fat depot has a unique inflammatory profile. Obesity 2010; 18: 879-883
- Gustafson B, Gogg S, Hedjazifar S et al. Inflammation and impaired adipogenesis in hypertrophic obesity in man. Am J Physiol Endocrinol Metab 2009; 297: 999-1003
- Paulson QX, Hong J, Holcomb VB et al. Effects of body weight and alcohol consumption on insulin sensitivity. Nutr J 2010; 22: 9-14
- Solomon TP, Sistrun SN, Krishnan RK et al. Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults. J Appl Physiol 2008; 104: 1313-1319
- Fisher-Posovszky P, Wabitsch M, Zochberg Z. Endocrinology of adipose tissue â€“ An update. Horm. Metab. Res 2007; 39: 314-321
- Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93: 64-73
- Rabe K, Lehrke M, Parhofer KG, Broedl UC (2008) Adipokines and insulin resistance. Mol. Med 2008; 14: 741-751
- Esteve E, Ricart W, Fernandez-Real JM Adipocytiknes and insulin resistance. The possible role of lipocalin-2, reginol binding protein-4 and adiponectin. Diabetes Care 2009; 32: 362-367
- Graham TE, Yang Q, BlÃ¼her M, et al. Retinol Binding protein 4 and insulin resistance in lean, obese and diabetic subjects. N Engl J Med 2006; 354: 2552-2563
- KlÃ¶ting N, Hraham TE, Berndt J et al. Serum retinol binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 2007; 6: 79-87
- BajzovÃ¡ M, KovÃ¡cikovÃ¡, VÄtkovÃ¡ M et al. Retinol-binding protein 4 expression in visceral and subcutaneous fat in human obesity. Physiol Res 2008; 57: 927-934
- Ost A, Danielsson A, LidÃ©n M et al. Retinol binding protein 4 attenuates insulin-induced phosphorylation or IRS and ERK1/2 in primary human adipocytes. FASEB J 2007; 21: 3693-3704
- Munkhtulga L, Nagashima S, Nakayama K et al. Regulatory SNP in the RBP4 gene modified the expression in adipocytes and associated with BMI. Obesity 2010; 18: 1006-1014
- Van Hoek M, Dehghan A, Zillikens MC et al. An RBP4 promoter polymorphism increases risk of type 2 diabetes. Diabetologia 2008; 51: 1423-1428
- Wu Y, Li H, Loos RJ et al. RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans. J Lipid Res 2009; 50: 1479-1486
- Kovacs P, Geyer M, Berndt J et al. Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression. Diabetes 2007; 56: 3095-3100
- Hu C, Jia W, Zhang R et al. Effect of RBP4 gene variants on circulating RBP4 concentration and type 2 diabetes in a Chinese population. Diabet Med. 2008; 25: 11-18
- Ruano M, Silvestre V, Castro R, et al. HOMA, QUICKI and MFfm to measure insulin resistance in morbid obesity. Obes Surg 2006; 16: 549-553
- Pffafl M W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: 2002-2007
Cite this Article:
International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.