title: [Interaction between environment and genetic background in type 2 diabetes: lessons from animal models].
abstract: The respective roles of predisposing genetic factors and environmental factors in the development of type 2 diabetes (T2D) in obese subjects is poorly documented. Rodent models have been set up in an attempt to better understand of the differential effect of a prolonged metabolic stress induced by a high fat diet on glycaemic control according to the genetic background. In utero growth retardation resulting from a hypocaloric diet in pregnant rats induces a dramatic alteration of the development of islet cells leading to diabetes and insulin secretory defects in adult age. Experimentally induced diabetes in rodents results in hyperglycaemia and hyperinsulinemia in the fetus related to accelerated endocrine pancreas maturation responsible for the onset of diabetes in the adult. Deranged metabolic environment during fetal life may therefore further contribute to the onset of diabetes in the adult. Normal mouse strains with different genetic backgrounds show a wide range of responses to a high fat diet, with strains resistant to the diet and other more or less sensitive to the diet, the most sensitive exhibiting obesity diabetes and, insulin deficiency. The inability of the β cell to respond to the increased insulin demand related to insulin resistance seems to be pivotal in the pathophysiologic process and a new notion is emerging: "nutritional genetics" which studies the influence of nutrients on gene expression.
authors.affiliation: Division de recherche sur les maladies métaboliques, Institut de recherches Servier, Suresnes, France. catherine.bernard@fr.netgrs.com
authors.forename: Catherine
authors.initials: C
authors.lastname: Bernard
authors.forename: Odile
authors.initials: O
authors.lastname: Della Zuana
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D002149:Energy Intake; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D005602:France / Q000453:epidemiology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats