title: Increased susceptibility to streptozotocin and impeded regeneration capacity of beta-cells in adult offspring of malnourished rats.
abstract: BACKGROUND
  Epidemiological studies related poor maternal nutrition and subsequent growth retardation in the progeny to the development of diabetes later in life. Low-protein diet during gestation altered the beta-cell development of the rat progeny by decreasing beta-cell proliferation and increasing their sensitivity to nitric oxide and cytokines in the foetus. This disturbed maternal environment had long-lasting consequences because the higher beta-cell vulnerability was maintained at adulthood.
  
  
  OBJECTIVE
  The aim of this study was to determine whether early malnutrition influences the vulnerability and the regeneration capacity of beta-cells after streptozotocin (STZ) damage at adulthood.
  
  
  METHODS
  Gestating rats were fed either a control or a low-protein diet until weaning. Adult female offspring received injections of Freund's adjuvant weekly for 5 weeks followed 24 h later by STZ. Half of the cohort was killed at d34, whereas the other half was maintained until d48 to analyse the regeneration capacity of the beta-cells.
  
  
  RESULTS
  Although control and low-protein rats had equivalent pancreatic insulin content and beta-cell volume density at d34, hyperglycaemia appeared earlier and was more dramatic in low-protein rats than in control rats. STZ treatment increased beta-cell proliferation similarly in both groups. At d48, apoptotic rate was higher in the low-protein group. Regeneration appeared in control, but not in the low-protein rats, where beta-cell aggregates/surface area and Reg1-positive area were decreased compared to control.
  
  
  CONCLUSIONS
  Maternal malnutrition programmes a more vulnerable endocrine pancreas in the progeny which is unable to regenerate after injury, therefore predisposing it to develop glucose intolerance and diabetes later in life.
authors.affiliation: Laboratory of Cell Biology, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Goosse
authors.forename: T
authors.initials: T
authors.lastname: Bouckenooghe
authors.forename: G
authors.initials: G
authors.lastname: Sisino
authors.forename: S
authors.initials: S
authors.lastname: Aurientis
authors.forename: C
authors.initials: C
authors.lastname: Remacle
authors.forename: B
authors.initials: B
authors.lastname: Reusens
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D005260:Female; D048070:Fetal Nutrition Disorders / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D013311:Streptozocin
keywords: beta-cell regeneration; diabetes; foetal programming; low-protein diet; streptozotocin