The Intrauterine Metabolic Environment Modulates the Gene Expression Pattern in Fetal Rat Islets: Prevention by Maternal Taurine Supplementation

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2008 Mar 4

PMID 18311556

Citations 12

Authors

B Reusens

T Sparre

L Kalbe

T Bouckenooghe

N Theys

M Kruhoffer

T F Orntoft

J Nerup

C Remacle

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes.

Methods: Pregnant Wistar rats were fed an LP diet (8% [wt/wt] protein) supplemented or not with taurine in the drinking water or a control diet (20% [wt/wt] protein). At 21.5 days of gestation, fetal pancreases were removed, digested and cultured for 7 days. Neoformed islets were collected and transcriptome analysis was performed.

Results: Maternal LP diet significantly changed the expression of more than 10% of the genes. Tricarboxylic acid cycle and ATP production were highly targeted, but so too were cell proliferation and defence. Maternal taurine supplementation normalised the expression of all altered genes.

Conclusions/interpretation: Development of the beta cells and particularly their respiration is modulated by the intrauterine environment, which may epigenetically modify expression of the genome and programme the beta cell towards a pre-diabetic phenotype. This mis-programming by maternal LP diet was prevented by early taurine intervention.

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References

Dumortier O, Blondeau B, Duvillie B, Reusens B, Breant B, Remacle C . Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia. 2007; 50(12):2495-503. DOI: 10.1007/s00125-007-0811-0. View

Schuit F, de Vos A, Farfari S, Moens K, Pipeleers D, Brun T . Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem. 1997; 272(30):18572-9. DOI: 10.1074/jbc.272.30.18572. View

Aerts L, Van Assche F . Animal evidence for the transgenerational development of diabetes mellitus. Int J Biochem Cell Biol. 2005; 38(5-6):894-903. DOI: 10.1016/j.biocel.2005.07.006. View

Tang C, Han P, Oprescu A, Lee S, Gyulkhandanyan A, Chan G . Evidence for a role of superoxide generation in glucose-induced beta-cell dysfunction in vivo. Diabetes. 2007; 56(11):2722-31. DOI: 10.2337/db07-0279. View

Hales C, Barker D, Clark P, Cox L, Fall C, Osmond C . Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991; 303(6809):1019-22. PMC: 1671766. DOI: 10.1136/bmj.303.6809.1019. View

Withers D, Burks D, Towery H, Altamuro S, Flint C, White M . Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet. 1999; 23(1):32-40. DOI: 10.1038/12631. View

Sturman J . Taurine in development. Physiol Rev. 1993; 73(1):119-47. DOI: 10.1152/physrev.1993.73.1.119. View

Boloker J, Gertz S, Simmons R . Gestational diabetes leads to the development of diabetes in adulthood in the rat. Diabetes. 2002; 51(5):1499-506. DOI: 10.2337/diabetes.51.5.1499. View

Taylor P, McConnell J, Khan I, Holemans K, Lawrence K, Asare-Anane H . Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol. 2004; 288(1):R134-9. DOI: 10.1152/ajpregu.00355.2004. View

10.

Cherif H, Reusens B, Ahn M, Hoet J, Remacle C . Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet. J Endocrinol. 1998; 159(2):341-8. DOI: 10.1677/joe.0.1590341. View

11.

Hill D, Petrik J, Arany E . Growth factors and the regulation of fetal growth. Diabetes Care. 1998; 21 Suppl 2:B60-9. View

12.

Sparre T, Reusens B, Cherif H, Larsen M, Roepstorff P, Fey S . Intrauterine programming of fetal islet gene expression in rats--effects of maternal protein restriction during gestation revealed by proteome analysis. Diabetologia. 2003; 46(11):1497-511. DOI: 10.1007/s00125-003-1208-3. View

13.

Garofano A, Czernichow P, Breant B . In utero undernutrition impairs rat beta-cell development. Diabetologia. 1998; 40(10):1231-4. DOI: 10.1007/s001250050812. View

14.

McMillen I, Robinson J . Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85(2):571-633. DOI: 10.1152/physrev.00053.2003. View

15.

Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K . Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J. 2002; 21(23):6581-9. PMC: 136959. DOI: 10.1093/emboj/cdf656. View

16.

Hales C, Barker D . The thrifty phenotype hypothesis. Br Med Bull. 2002; 60:5-20. DOI: 10.1093/bmb/60.1.5. View

17.

Dahri S, Snoeck A, Remacle C, Hoet J . Islet function in offspring of mothers on low-protein diet during gestation. Diabetes. 1991; 40 Suppl 2:115-20. DOI: 10.2337/diab.40.2.s115. View

18.

Nielsen K, Kruhoffer M, Orntoft T, Sparre T, Wang H, Wollheim C . Gene expression profiles during beta cell maturation and after IL-1beta exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1beta sensitivity. Diabetologia. 2004; 47(12):2185-99. DOI: 10.1007/s00125-004-1578-1. View

19.

Han J, Bae J, Kim S, Lee H, Jang B, Lee I . Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism. Am J Physiol Endocrinol Metab. 2004; 287(5):E1008-18. DOI: 10.1152/ajpendo.00008.2004. View

20.

Tiedge M, Lortz S, Drinkgern J, Lenzen S . Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes. 1997; 46(11):1733-42. DOI: 10.2337/diab.46.11.1733. View