title: Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.
abstract: Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway.
authors.affiliation: Mestrado em Biociências, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Boa Esperança, Cuiaba, MT, Brazil.
authors.forename: Letícia Martins
authors.initials: LM
authors.lastname: Ignácio-Souza
authors.forename: Sílvia Regina
authors.initials: SR
authors.lastname: Reis
authors.forename: Vanessa Cristina
authors.initials: VC
authors.lastname: Arantes
authors.forename: Bárbara Laet
authors.initials: BL
authors.lastname: Botosso
authors.forename: Roberto Vilela
authors.initials: RV
authors.lastname: Veloso
authors.forename: Fabiano
authors.initials: F
authors.lastname: Ferreira
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
authors.forename: Everardo Magalhães
authors.initials: EM
authors.lastname: Carneiro
authors.forename: Marise Auxiliadora de Barros
authors.initials: MA
authors.lastname: Reis
authors.forename: Márcia Queiroz
authors.initials: MQ
authors.lastname: Latorraca
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D016640:Diabetes, Gestational / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000627:therapeutic use; D005260:Female; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007774:Lactation; D044342:Malnutrition / Q000178:diet therapy / Q000503:physiopathology*; D039382:Maternal Nutritional Physiological Phenomena; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects; D014886:Weaning
chemical_list: D004044:Dietary Proteins; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D011493:Protein Kinase C; D005947:Glucose