Programming of Impaired Insulin Secretion Versus Sensitivity: Cause or Effect?

  • Brigitte Reusens
  • Claude Remacle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 646)

A substantial body of evidence suggests that a poor intrauterine milieu elicited by maternal nutritional disturbance, including maternal diabetes or placental insufficiency, may programme susceptibility in the fetus to later development of glucose intolerance and diabetes. Numerous data in animals have allowed possible mechanisms for programming to be proposed. This review of work in several animal models attempts to identify the cellular and molecular mechanisms at the level of the beta-cell and in the insulin sensitive tissues that are involved in the process of events leading to the pathology later in life.


Animal models beta cell diabetes early programming insulin target tissues 


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  1. Aerts, L. and A. Van Assche (2006). “Animal evidence for the transgenerational development of diabetes mellitus”. Int J Biochem Cell Biol 38(5–6): 894–903.PubMedCrossRefGoogle Scholar
  2. Blondeau, B., J. Lesage, P. Czernichow, J.P. Dupouy and B. Breant (2001). “Glucocorticoids impair fetal beta-cell development in rats”. Am J Physiol Endocrinol Metab 281(3): E592–E599.PubMedGoogle Scholar
  3. Boloker J., S.J. Gertz and R.A. Simmons (2002). “Gestational diabetes leads to the development of diabetes in adulthood in the rat”. Diabetes 51(5): 1499–1506.PubMedCrossRefGoogle Scholar
  4. Boujendar, S., E. Arany, D. Hill, C. Remacle and B. Reusens (2003). “Taurine supplementation of a low protein diet fed to rat dams normalized the vascularization of the fetal endocrine pancreas”. J Nutr 133(9): 2820–2825.PubMedGoogle Scholar
  5. Butler A.E., J. Janson, S. Bonner-Weir, R. Ritzel, R.A. Rizza and P.C. Butler (2003). “Beta-cell deficit and increased beta-cell apoptosis in human with type 2 diabetes”. Diabetes 52(1): 102–110.PubMedCrossRefGoogle Scholar
  6. Cherif, H., B. Reusens, S. Dahri and C. Remacle (2001). “A protein restricted diet during pregnancy alters in vitro insulin secretion from islets of fetal Wistar rats”. J Nutr 131(5): 1555–1559.PubMedGoogle Scholar
  7. Dabelea D., W.C. Knowler and D.J. Pettitt (2000). “Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians” J Mat Fetal Med 9(1): 83–88.Google Scholar
  8. Dahri, S., A. Snoeck, B. Reusens, C Remacle and J.J. Hoet (1991). “Islet function in offspring of mothers on low protein diet during gestation”. Diabetes 40(suppl 2): 115–120.PubMedGoogle Scholar
  9. Garofano, A., P. Czernichow and B. Bréant (1997). “In utero undernutrition impairs rat β-cell development”. Diabetologia 40(10): 1231–1234.PubMedCrossRefGoogle Scholar
  10. Garofano, A., P. Czernichow and B. Bréant (1998). “Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat”. Diabetologia 41(9): 1114–1120.PubMedCrossRefGoogle Scholar
  11. Hales, C.N., D.J. Barker, P.M. Clark, L.J. Cox, C. Fall, C. Osmond and P.D. Winter (1991). “Fetal and infant growth and impaired glucose tolerance at age 64.” BMJ 303(6809): 1019–1022.PubMedCrossRefGoogle Scholar
  12. Innes K.E., T.E. Byers, J.A. Marshall, A. Baron, M. Orleans and R.F. Hamman (2002). “Association of a woman's own birth weight with subsequent risk for gestational diabetes.” JAMA 287(19): 2534–2541.PubMedCrossRefGoogle Scholar
  13. Leahy, J. (2005). “Pathogenesis of type 2 diabetes mellitus”. Arch Med Res 36(3): 197–209.PubMedCrossRefGoogle Scholar
  14. Merezak, S., B. Reusens, M.T. Ahn and C. Remacle (2004). “Effect of maternal low protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines”. Diabetologia 47(4): 669–675.PubMedCrossRefGoogle Scholar
  15. Molsted-Pedersen, L.L., J. Wagner, L. Klebe and J. Pedersen (1972). “Aspects of carbohydrate metabolism in newborn infants of diabetic mothers. IV. Neonatal changes in plasma free fatty acid concentration.” Acta Endocrinol 71: 338–345.PubMedGoogle Scholar
  16. Ozanne, S.E., M.W. Dorling, C.L. Wang and B.T. Nave (2001). “Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats”. Am J Physiol 280(3): E534–E539.Google Scholar
  17. Ozanne, S.E., G.S. Olsen, L.L. Hansen, K.J. Tingey, B.T. Nave, C.L.Wang, K. Hartil, C.J. Petry and L. Mosthaf-Seedorf (2003). “Early growth restriction leads to down regulation of protein kinase C zeta and insulin resistance in skeletal muscle”. J Endocrinol 177(2): 235–241.PubMedCrossRefGoogle Scholar
  18. Ozanne, S.E., C.B. Jensen, K.J. Tingey, H. Stogaard, S. Madbad and A.A. Vaag (2005). “Low birth weight is associated with specific changes in muscle insulin-signalling protein expression”. Diabetologia 48(3): 547–552.PubMedCrossRefGoogle Scholar
  19. Peterside, I.E., M.A. Selak and R.A. Simmons (2003). “Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats”. Am J Physiol Endocrinol Metab 285(6): 1258–1266.Google Scholar
  20. Petrik, J., B. Reusens, E. Arany, C. Remacle, C. Coelho, J.J. Hoet and D. Hill (1999). “A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor II”. Endocrinology 140(10): 4861–4873.PubMedCrossRefGoogle Scholar
  21. Petry, C.J., M.W. Dorling, D.B. Pawlak, S. Ozanne and C.N. Hales (2001). “Diabetes in old male offspring of rat dams fed a reduced protein diet”. Int J Ex Diabetes Res 2(2): 139–143.CrossRefGoogle Scholar
  22. Ravelli A.C., J.H. van der Meulen, R.P. Michels, C. Osmond, D.J. Barker, C.N. Hales and O.P. Bleker (1998). “Glucose tolerance in adults after prenatal exposure to famine.” Lancet 351 (9097): 173–177.PubMedCrossRefGoogle Scholar
  23. Reusens, B. and C. Remacle (2001). “Intergenerational effects of adverse intrauterine environment on perturbation of glucose metabolism”. Twin Res 4(5): 406–411.PubMedCrossRefGoogle Scholar
  24. Rich-Edwards, J.W., G.A. Colditz, M.J. Stampfer, W.C. Willett, M.W. Gilman, C.H. Hennenkens, F.E. Speizer and J.E. Manson (1999). “Birth-weight and the risk for type 2 diabetes mellitus in adult women.” Ann Int Med 130: 278–284.PubMedGoogle Scholar
  25. Simmons, R.A., I. Suponisky-Kroyter and M.A. Selak (2005). “Progressive accumulation of mitochondrial DNA mutations and decline in mitochondrial function lead to beta-cell failure”. J Biol Chem 280(31): 28785–28791.PubMedCrossRefGoogle Scholar
  26. Snoeck, A., C. Remacle, B. Reusens and J.J. Hoet, (1990). “Effect of low protein diet during pregnancy on the fetal rat endocrine pancreas”. Biol Neonate 57(2): 107–118.PubMedCrossRefGoogle Scholar
  27. Sparre, T., B. Reusens, H. Cherif, M.R. Larsen, P. Roepstorff, S.J. Fey, P. Mose Larsen, C. Remacle and J. Nerup (2003). “Intrauterine programming of fetal islet gene expression in rats — effects of maternal protein restriction during gestation revealed by proteome analysis”. Diabetologia 46(11): 1497–1511.PubMedCrossRefGoogle Scholar
  28. Srinivasan M., S.D. Katewa, A. Palaniyappan, J.D. Pandya and M. Patel (2006). “Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood”. Am J Physiol Endocrinol Metab 291: E792–E799.PubMedCrossRefGoogle Scholar
  29. Taylor, P.D., J. McConnell, I.Y. Khan, K. Holemans, K.M. Lawrence, H. Asare-Anane, S.J. Persaud, P. Jones, L. Petrie, M Hanson and L. Poston (2005). “Impaired glucose homeostasis and mito-chondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy”. Am J Physiol Regul Integr Comp Physiol 288(1): R134–R139.PubMedGoogle Scholar
  30. Tiedge, M., S. Lortz, J. Drinkgern and S Lenzen (1997). “Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells”. Diabetes 46(11): 1733–1742.PubMedCrossRefGoogle Scholar
  31. Van Assche, F.A., F. De Prins, L. Aerts and M. Verjans (1977). “The endocrine pancreas in small for date infants.” Brit J Obst Gynaec 84(10): 751–753.Google Scholar
  32. Vickers, M.H., B.H. Breier, W.S. Cutfield, P.L. Hofman and P.D. Gluckman (2000). “Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition”. Am J Physiol Endocrinol Metab 279(1): E83–E87.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2009

Authors and Affiliations

  1. 1.Laboratoire de Biologie Cellulaire, Institut des Sciences de la VieUniversité catholique de LouvainBelgique

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