Consequências da restrição proteica na vida intrauterina e na lactação sobre as adaptações na morfologia de ilhotas pancreáticas durante a prenhez

Abstract

The population of pancreatic -cells is dynamic and susceptible to compensatory changes to maintenance of glucose levels within a narrow range. The -cells mass adapts under various pathological and physiological conditions. Protein restriction during foetal and neonatal development produces major structural changes in the size, shape and composition of islets, which remain after nutritional recovery. Pregnancy alter the balance between mechanisms that increase (hypertrophy, proliferation, neogenesis and transdifferentiation) and reduce (atrophy, apoptosis, necrosis and autophagy) the number and size of -cells. Thus, we evaluated whether early life protein restriction alters mechanisms that produce and reduce the size and number of-cells, compromising the islet structure during the first two-thirds (15th d) and at the end (20th d) of pregnancy in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats from foetal to adult life as well as in protein-restricted rats that recovered after weaning (RP and RNP). On the 15th d of pregnancy, the distribution of islets smaller and larger than the median was similar in the RP, RNP, LPP and LPNP groups. The CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. Pregnancy enhanced the -cell proliferation frequencies independent of nutritional status. The apoptosis frequency increased in the RP and RNP groups compared to other groups. Pregnancy did not affect the transdifferentiation frequency, but increased the neogenesis frequency, regardless of the nutritional status. On the 20th d of pregnancy, a higher proportion of islets smaller than the median was observed in the RNP, LPNP and CNP groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. The -cell proliferation frequency was lower in recovered rats compared to low protein and control rats. Apoptosis was higher in recovered rats than in the low-protein and control groups. Neogenesis was similar in pregnant rats. Thus, protein malnutrition in early life changed the size of the islets in the first two-thirds of pregnancy, reflecting, at least in part, the increase of -cell apoptosis.