Abstract
Gestational diabetes mellitus (GDM) is associated with increased insulin resistance and a heightened level of oxidative stress (OS). Additionally, high iron consumption could also increase insulin resistance and OS, which could aggravate GDM risk. The aim of this study is to evaluate a high fructose diet (F) as an alternative experimental model of GDM on rats. We also have evaluated the worst effect of a fructose iron-enriched diet (FI) on glucose tolerance and OS status during pregnancy. Anthropometric parameters, plasma glucose levels, insulin, and lipid profile were assessed after delivery in rats fed an F diet. The effects observed in mothers (hyperglycemia, and hyperlipidemia) and on pups (macrosomia and hypoglycemia) are similar to those observed in women with GDM. Therefore, the fructose diet could be proposed as an experimental model of GDM. In this way, we can compare the effect of an iron-enriched diet on the metabolic and redox status of mother rats and their pups. The mothers’ glycemic was similar in the F and FI groups, whereas the glycemic was significantly different in the newborn. In rat pups born to mothers fed on an FI diet, the activities of the antioxidant enzyme glutathione peroxidase (GPx) and glutathione-S-transferase in livers and GPx in brains were altered and the gender analysis showed significant differences. Thus, alterations in the glycemic and redox status in newborns suggest that fetuses are more sensitive than their mothers to the effect of an iron-enriched diet in the case of GDM pregnancy. This study proposed a novel experimental model for GDM and provided insights on the effect of a moderate iron intake in adding to the risk of glucose disorder and oxidative damage on newborns.
Similar content being viewed by others
References
ADA, American Diabetes Association (2003) Position statement. Gestational diabetes mellitus. Diabetes Care 26(Suppl 1):S103–S105
Marcinkevagea JA, Narayan KM (2011) Gestational diabetes mellitus: taking it to heart. Prim Care Diabetes 5:81–88
Leiva A, Pardo F, Ramírez MA, Farías M, Casanello P, Sobrevia L (2011) Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy. Exp Diabetes Res. doi:10.1155/2011/349286
Harlev A, Wiznitzer A (2010) New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep 10:242–247
ADA American Diabetes Association (2007) Diagnosis and classification of diabetes mellitus. Diabetes Care 30(Suppl 1):42–47
Lappas M, Hiden U, Desoye G, Froehlich J, Hauguel-de Mouzon S, Jawerbaum A (2011) The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antioxid Redox Signal 15:3061–3100
Zein S, Rachidi S, Hininger-Favier I (2014) Is oxidative stress induced by iron status associated with gestational diabetes mellitus? J Trace Elem Med Biol 28:65–69
Gelaleti RB, Damasceno DC, Lima OPH, Salvadori FDM, Calderon IP, Peraçoli JC, Rudge MVC (2015) Oxidative DNA damage in diabetic and mild gestational hyperglycemic pregnant women. Diabetol Metab Syndr. doi:10.1186/1758-5996-7-1
Shang M, Zhao J, Yang L, Lin L (2015) Oxidative stress and antioxidant status in women with gestational diabetes mellitus diagnosed by IADPSG criteria. Diabetes Res Clin Pract 109(2):404–410
Robertson RP (2004) Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 279:42351–42354
Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440(7086):944–948
Damasceno DC, Netto AO, Iessi IL, Gallego FQ, Corvino SB, Dallaqua B, Sinzato YK, Bueno A, Calderon IMP, Rudge MVC (2014) Streptozotocin-induced diabetes models: pathophysiological mechanisms and fetal outcomes. Biomed Res Int. doi:10.1155/2014/819065
Caluwaerts S, Holemans K, Van Bree R, Verhaeghe J, Van Assche FA (2003) Is low-dose streptozotocin in rats an adequate model for gestational diabetes mellitus? J Soc Gynecol Investig 10:216–221
Kiss A, Lima P, Sinzato Y, Takaku M, Takeno M, Rudge M, Damasceno D (2009) Animal models for clinical and gestational diabetes: maternal and fetal outcomes. Diabetol Metab Syndr. doi:10.1186/1758-5996-1-21
Tian ZH, Miao FT, Zhang X, Wang QH, Lei N, Guo LC (2015) Therapeutic effect of okra extract on gestational diabetes mellitus rats induced by streptozotocin. Asian Pac J Trop Med 8(12):1038–1042
Busserolles J, Gueux E, Rock E, Demigne C, Mazur A, Rayssiguier Y (2003) Oligofructoseprotects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J Nutr 133:1903–1908
Kolderup A, Svihus B (2015) Fructose metabolism and relation to atherosclerosis, type 2 diabetes, and obesity. J Nutr Metab. doi:10.1155/2015/823081
Hansen JB, Moen IW, Mandrup-Poulsen T (2014) Iron: the hard player in diabetes pathophysiology. Acta Physiol 210:717–732
Bao W, Rong Y, Rong S, Liu L (2012) Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis. BMC Med. doi:10.1186/1741-7015-10-119
Bo S, Menato G, Villois P, Gambino R, Cassader M, Cotrino I, Cavallo-Perin P (2009) Iron supplementation and gestational diabetes in midpregnancy. Am J Obstet Gynecol 201(2):158 e1-6
Bowers K, Yeung E, Williams MA, Qi L, Tobias DK, Hu FB, Zhang CL (2011) A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus. Diabetes Care 34:1557–1563
Qiu CF, Zhang CL, Gelaye B, Enquobahrie DA, Frederick IO, Williams MA (2011) Gestational diabetes mellitus in relation to maternal dietary heme iron and nonheme iron intake. Diabetes Care 34:1564–1569
Fernandez-Real JM, Lopez-Bermejo A, Ricart W (2002) Cross-talk between iron metabolism and diabetes. Diabetes 51:2348–2354
Swaminathan S, Fonseca VA, Alam MG, Shah SV (2007) The role of iron in diabetes and its complications. Diabetes Care 30:1926–1933
Khambalia AZ, Collins CE, Roberts CL, Morris JM, Powell KL, Tasevski V, Nassar N (2016) Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes. Eur J Clin Nutr 70(3):358–363
Goldstein BJ, Mahadev K, Wu X, Zhu L, Motoshima H (2005) Role of insulin-induced reactive oxygen species in the insulin signaling pathway. Antioxid Redox Signal 7(7–8):1021–1023
Casanueva E, Viteri FE (2003) Iron and oxidative stress in pregnancy. J Nutr 133:1700S–1708S
Richard MJ, Portal B, Meo J, Coudray C, Hadjian A, Favier A (1992) Malondialdehyde kit evaluated for determining plasma and lipoprotein fractions that react with thiobarbituric acid. Clin Chem 38:704–709
Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76
Faure P, Lafond JL (1995) Measurement of plasma sulfhydryl and carbonyl groups as a possible indicator of protein oxydation. In: Favier AE, Cadet J, Kalnyanaraman M, Fontecave M, Pierre JL (eds) Analysis of free radicals in biological systems. Birkäuser, Berlin, pp. 237–248
Akerboom TP, Sies H (1981) Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 77:373–382
Gunzler WA, Kremers H, Flohe L (1974) An improved coupled test procedure for glutathione peroxidase (EC 1.11.1.9.) in blood. Z Klin Chem Klin Biochem 12:444–448
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, Agrawal YO (2016) Challenges and issues with streptozotocin-induced diabetes—a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact 25:244 49-63
Hininger-Favier I, Benaraba R, Coves S, Anderson RA, Roussel AM (2009) Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat. J Am Coll Nutr 28:355–361
Damasceno DC, Volpato GT, Calderon IP, Rudge MVC (2002) Oxidative stress and diabetes in pregnant rats. Anim Reprod Sci 72:235–244
Kc K, Shakya S, Zhang H (2015) Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 66(suppl 2):14–20
Harper LM, Tita A, Biggio JR (2015) The institute of medicine guidelines for gestational weight gain after a diagnosis of gestational diabetes and pregnancy outcomes. Am J Perinatol 32(3):239–246
Couturier K, Qin B, Batandier C, Awada M, Hininger-Favier I, Canini F, Leverve X, Roussel AM, Anderson RA (2011) Cinnamon increases liver glycogen in an animal model of insulin resistance. Metabolism 60:1590–1597
Lin WJ, Kirksey A (1976) Effects of different levels of dietary iron on pregnancy superimposed upon growth in the rat. J Nutr 106:543–554
Ward RJ, Wilmet S, Legssyer R, Crichton RR (2003) Iron supplementation during pregnancy-a necessary or toxic supplement ? Bioinorg Chem Appl 1(2):169–176
Vilà L, Roglans N, Perna V, Sánchez RM, Vázquez-Carrera M, Alegret M, Laguna JC (2011) Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose. J Nutr Biochem 22(8):741–751
Rodríguez L, Otero P, Panadero MI, Rodrigo S, Álvarez-Millán JJ, Bocos C (2015) Maternal fructose intake induces insulin resistance and oxidative stress in male, but not female, offspring. J Nutr Metab 2015 (Article ID 158091):8. doi:10.1155/2015/158091
Sampaio AFS, Silva M, Dornas WC, Costa DC, Silva ME, dos Santos RC, de Lima WG, Pedrosa ML (2014) Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes. Biometals 27(2):349–361
Kobayashi H, Matsuda M, Fukuhara A, Komuro R, Shimomura I (2009) Dysregulated glutathione metabolism links to impaired insulin action in adipocytes. Am J Physiol Endocrinol Metab 296:E1326–E1334
Kruse MS, Vega MC, Rey M, Coirini H (2014) Sex differences in LXR expression in normal offspring and in rats born to diabetic dams. J Endocrinol. doi:10.1530/JOE-14-0054
Aouacheri O, Saka S, Krim M, Messaadia A, Maidi I (2015) The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus. Can J Diabetes 39:44–49
De Haan JB, Cristiano F, Iannello RC, Kola I (1995) Cu/Zn-superoxide dismutase and glutathione peroxidase during aging. Biochem Mol Biol Int 35:1281–1297
Perluigi M, Butterfield DA (2012) Oxidative stress and down syndrome: a route toward Alzheimer-like dementia. Curr Gerontol Geriatr Res 72:490–494
Berggren KL, Chen J, Fox J, Miller J, Dodds L, Dugas B, Vargas L, Lothian A, McAllum E, Volitakis I, Roberts B, Bush AI, Fox JH (2015) Neonatal iron supplementation potentiates oxidative stress, energetic dysfunction and neurodegeneration in the R6/2 mouse model of Huntington’s disease. Redox Biol 4:363–374
Mason RP, Casu M, Butler N, Breda C, Campesan S, Clapp J, Green EW, Dhulkhed D, Kyriacou CP, Giorgini F (2013) Glutathione peroxidase activity is neuroprotective in models of Huntington’s disease. Nat Genet 45:1249–1254
Kim CH, Kim HK, Bae SJ, Park JY, Lee KU (2011) Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women. Metabolism 60(3):414–420
Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30(6):445–600
Madra S, Mann F, Francis JE, Manson MM, Smith AG (1996) Modulation by iron of hepatic microsomal and nuclear cytochrome P450, and cytosolic glutathione S-transferase and peroxidase in C57BL/10ScSn mice induced with polychlorinated biphenyls (Aroclor 1254). Toxicol Appl Pharmacol 136(1):79–86
Rodríguez L, Panadero MI, Roglans N, Otero P, Álvarez-Millán JJ, Laguna JC, Bocos C (2013) Fructose during pregnancy affects maternal and fetal leptin signaling. J Nutr Biochem 24(10):1709–1716
Acknowledgments
We would like to thank the Rectorat of the Lebanese University, Beirut-Lebanon, to support this work.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All experimental procedure was reviewed and approved by the Joseph Fourier University Institutional Ethic Committee for Animal Experiment. The rats were maintained and handled in agreement with the Guide for the Care and Use of Laboratory Animals.
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Zein, S., Sitti, F., Osman, M. et al. Middle Iron-Enriched Fructose Diet on Gestational Diabetes Risk and on Oxidative Stress in Offspring Rats. Biol Trace Elem Res 175, 405–413 (2017). https://doi.org/10.1007/s12011-016-0791-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-016-0791-3