Nutrient-Induced Maternal Hyperinsulinemia and Metabolic Programming in the Progeny Mulchand S. Patel a , Malathi Srinivasan a , and Suzanne G. Laychock b Departments of a Biochemistry and b Pharmacology and Toxicology, School of Medicine, State University of New York at Buffalo, Buffalo, N.Y., USA Fetal Programming due to an Altered Nutritional Experience in utero Although the early development of living creatures is primarily influenced by the genetic instructions acquired at the time of conception, the environment under which the organism develops limits the expression of these genetic instructions. Fetal and neonatal growth in mammals is a complex process involving cross talk between the fetal genome, the maternal intrauterine envi- ronment and the early postnatal nutritional experience. Hence the well-being of the mother (with optimal nutrition) during pregnancy is of pivotal impor- tance for optimal growth of the fetus and, in this context, the quality and quantity of nutrition in the mother have been identified as important factors contributing to the metabolic programming of the fetus. Metabolic program- ming is the phenomenon by which a nutritional stress/stimulus overlapping with the critical window of early development of specific organs permanently alters the physiology and metabolism of the organism thereby predisposing it for adult-onset disease conditions. Several epidemiological studies have provided compelling evidence for the role of metabolic programming in the etiology of adult-onset diseases thereby emphasizing the importance of adequate nutrition during fetal development. The fetal origins hypothesis, first proposed by Barker, suggests that dispro- portionate size at birth of the newborn due to an adverse intrauterine environ- ment during pregnancy complicated with malnutrition (protein or caloric) is highly correlated with the increased incidence of cardiovascular diseases, type-2 diabetes and hypertension during later periods in life [1, 2]. Studies Hornstra G, Uauy R, Yang X (eds): The Impact of Maternal Nutrition on the Offspring. Nestlé Nutrition Workshop Series Pediatric Program, vol 55, pp 137–151, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2005. 137