title: Diabetes in the Cohen Rat Intensifies the Fetal Pancreatic Damage Induced by the Diabetogenic High Sucrose Low Copper Diet.
abstract: Intrauterine hyperglycemic environment could harm the fetus making it more susceptible to develop postnatal glucose intolerance. A possible mechanism is compromise of the fetal pancreatic development. We previously found that a high sucrose low copper diabetogenic diet induces type 2 diabetes in the Cohen diabetic sensitive rats, but not in the Sabra control rats. However, oxidative stress was observed in the placenta and term fetal liver of diabetic and nondiabetic controls. We now investigated whether the fetal pancreas is affected by this diet and whether the effects result from oxidative stress, maternal hyperglycemia, or both. Term fetal pancreases were evaluated for morphology, beta cells, oxidative stress, apoptosis, and DNA methylation. There were no microscopic changes in hematoxylin and eosin stained sections and beta cells immunostaining in the pancreas of fetuses of both strains. Fetuses of the sensitive strain fed diabetogenic diet had significantly higher activity of superoxide dismutase and catalase, elevated levels of low molecular weight antioxidants, and more intense immunostaining for nuclear factor kappa-B and hypoxia inducing factor-1α. Both strains fed diabetogenic diet had increased immunostaining for Bcl-2-like protein and caspase 3 and decreased immunostaining for 5-methylcytosine in their islets and acini. Our data suggest that maternal diabetogenic diet alters apoptotic rate and epigenetic steady states in the term fetal pancreas, unrelated to maternal diabetes. Maternal hyperglycemia further increases pancreatic oxidative stress, aggravating the pancreatic damage. The diet-induced insults to the fetal pancreas may be an important contributor to the high susceptibility to develop diabetes following metabolic intrauterine insults.
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.|Department of Neonatology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Zivanit
authors.initials: Z
authors.lastname: Ergaz
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Meytal
authors.initials: M
authors.lastname: Neeman-Azulay
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Liza
authors.initials: L
authors.lastname: Weinstein-Fudim
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.|Diabetes Unit, Department of Internal Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weksler-Zangen
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Shoshani-Dror
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Ornoy
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003300:Copper / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D004032:Diet / Q000009:adverse effects*; D005333:Fetus / Q000473:pathology*; D007150:Immunohistochemistry; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010179:Pancreas / Q000196:embryology* / Q000473:pathology*; D019518:Postprandial Period; D051381:Rats; D013395:Sucrose / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008315:Malondialdehyde; D013395:Sucrose; D044503:5-Methylcytosine; D003300:Copper
keywords: Rat; apoptosis; copper; fetus; gestational diabetes; global DNA methylation; oxidative stress; pancreas