In previous work, we demonstrated that a 65% protein calorie food restriction started during the third trimester of gestation in rats caused a reduced -cell mass at 4 days of life that persisted until adult age. In this study with adult undernourished (U) rats, we investigated 1) whether undernutrition affects the -cell growth potential and both -cell proliferation and differentiation and 2) the implication of the IGFs, highly responsive to nutritional status, in these processes. To this end, we used the 90% pancreatectomy (Px) procedure in U and control (C) adult rats. The results show that, on day 2 after Px, -cell replication was significantly higher in C rats, whereas the -cell neogenesis was markedly increased in U/Px rats. Both the serum levels of IGF-I and the liver IGF-I mRNA expression were reduced in adult U rats before and after Px compared with C rats. Pancreatic IGF-I mRNA expression was reduced in U animals on day 0. However, on day 2 after Px, the increase of pancreatic IGF-I mRNA expression was significantly higher in U rats than in C rats. These data suggest that -cells still have the capacity to regenerate in the adult U rats, with a higher efficiency than C rats on day 2, and that both -cell neogenesis and -cell replication are stimulated. The increased pancreatic IGF-I mRNA may be instrumental in these processes.-cell regeneration; proliferation; insulin-like growth factors DIETARY INFLUENCES DURING EARLY STAGES of development present a risk factor for the onset of both perinatal and later life diseases. As indicated by the "thrifty phenotype hypothesis" (23), the endocrine pancreas may be particularly susceptible to the effects of poor maternal nutrition, since fetal and postnatal periods are critical for -cell development and maturation of pancreatic function. In concert, several studies in experimental models with rats subjected to different patterns of malnutrition have reported that maternal food restriction significantly affects the -cell mass in the fetuses (2, 4, 49) and in the offspring neonates at day 1 (19) and day 4 of postnatal life (37). This effect persists until adulthood (37) and can provoke long-lasting consequences related to the plasticity of the endocrine pancreas under situations of increased insulin demand, such as aging (19) and pregnancy (5). However, to our knowledge, the effect of prolonged global malnutrition starting in the fetal period on the potential for regeneration of the pancreatic islets in adulthood has not been investigated.The adult pancreas has the capacity to respond to changing physiological needs such as the requirement for increased -cell mass/function during pregnancy, obesity, or insulin resistance and an ability to regenerate cells (both replication and neogenesis), including -cells, which has been convincingly demonstrated in animal models of pancreatic injury and diabetes (46,47). One of these models is the partial pancreatectomy in rats (7,11). In this model, the pancreatic regeneration involves, first, replication of preexisting ...