title: Islet inflammation, hemosiderosis, and fibrosis in intrauterine growth-restricted and high fat-fed Sprague-Dawley rats.
abstract: Prenatal and postnatal factors such as intrauterine growth restriction (IUGR) and high-fat (HF) diet contribute to type 2 diabetes. Our aim was to determine whether IUGR and HF diets interact in type 2 diabetes pathogenesis, with particular attention focused on pancreatic islet morphology including assessment for inflammation. A surgical model of IUGR (bilateral uterine artery ligation) in Sprague-Dawley rats with sham controls was used. Pups were fed either HF or chow diets after weaning. Serial measures of body weight and glucose tolerance were performed. At 25 weeks of age, rat pancreases were harvested for histologic assessment. The birth weight of IUGR pups was 13% lower than that of sham pups. HF diet caused excess weight gain, dyslipidemia, hyperinsulinemia, and mild glucose intolerance, however, this was not aggravated further by IUGR. Markedly abnormal islet morphology was evident in 0 of 6 sham-chow, 5 of 8 sham-HF, 4 of 8 IUGR-chow, and 8 of 9 IUGR-HF rats (chi-square, P = 0.007). Abnormal islets were characterized by larger size, irregular shape, inflammation with CD68-positive cells, marked fibrosis, and hemosiderosis. β-Cell mass was not altered by IUGR. In conclusion, HF and IUGR independently contribute to islet injury characterized by inflammation, hemosiderosis, and fibrosis. This suggests that both HF and IUGR can induce islet injury via converging pathways. The potential pathogenic or permissive role of iron in this process of islet inflammation warrants further investigation.
authors.affiliation: Australian National University Medical School, Australian National University, Acton, Australia.
authors.forename: Viviane
authors.initials: V
authors.lastname: Delghingaro-Augusto
authors.affiliation: Australian National University Medical School, Australian National University, Acton, Australia.
authors.forename: Leili
authors.initials: L
authors.lastname: Madad
authors.affiliation: Department of Anatomical Pathology, The Canberra Hospital, Garran, Australia.
authors.forename: Arin
authors.initials: A
authors.lastname: Chandra
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, Australia.
authors.forename: Charmaine J
authors.initials: CJ
authors.lastname: Simeonovic
authors.affiliation: Australian National University Medical School, Australian National University, Acton, Australia; Department of Anatomical Pathology, The Canberra Hospital, Garran, Australia; John Curtin School of Medical Research, Australian National University, Acton, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dahlstrom
authors.affiliation: Australian National University Medical School, Australian National University, Acton, Australia; Department of Endocrinology and Diabetes, The Canberra Hospital, Garran, Australia. Electronic address: christopher.nolan@anu.edu.au.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nolan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D050171:Dyslipidemias / Q000150:complications; D005215:Fasting / Q000097:blood; D005317:Fetal Growth Retardation / Q000473:pathology*; D005355:Fibrosis; D006486:Hemosiderosis / Q000150:complications* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006946:Hyperinsulinism / Q000150:complications; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D007515:Islets of Langerhans / Q000002:abnormalities / Q000473:pathology*; D008297:Male; D009929:Organ Size; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein