title: Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific.
abstract: Restriction of dietary protein during gestation and lactation in the rat results in a reduction in beta cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 microm(2)) and medium (between 5000 and 10 000 microm(2)) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of beta cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in mid-gestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both beta cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of beta cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of beta cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.
authors.affiliation: Lawson Health Research Institute, St Joseph's Health Care, 268 Grosvenor Street Room H404, London, Ontario, Canada N6A 4V2.
authors.forename: Astrid
authors.initials: A
authors.lastname: Chamson-Reig
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Thyssen
authors.forename: Edith
authors.initials: E
authors.lastname: Arany
authors.forename: David J
authors.initials: DJ
authors.lastname: Hill
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D051273:Glucose Transporter Type 2 / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000737:chemistry / Q000196:embryology; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D010179:Pancreas / Q000033:anatomy & histology* / Q000737:chemistry / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism
chemical_list: D004044:Dietary Proteins; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein