title: Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats.
abstract: ODM (offspring of diabetic mothers) have an increased risk of developing metabolic and cardiovascular dysfunction; however, few studies have focused on the susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg of body weight, intraperitoneally) in pregnant rats on gestational day 13 and was partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (P<0.05); however, by 6 months of age this trend had reversed. A euglycaemic-hyperinsulinamic clamp revealed insulin resistance in male ODM (P<0.05). In 6-8-month-old female ODM, aortas had significantly enhanced contractility in response to KCl, ET-1 (endothelin-1) and NA (noradrenaline). No differences in responses to ET-1 and NA were apparent with co-administration of L-NNA (NG-nitro-L-arginine). Relaxation in response to ACh (acetylcholine), but not SNP (sodium nitroprusside), was significantly impaired in female ODM. In contrast, males had no between-group differences in response to vasoconstrictors, whereas relaxation to SNP and ACh was greater in ODM compared with control animals. Thus the development of diabetes during pregnancy programmes gender-specific insulin resistance and vascular dysfunction in adult offspring.
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Segar
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Norris
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Yao
authors.forename: Shanming
authors.initials: S
authors.lastname: Hu
authors.forename: Stacia L
authors.initials: SL
authors.lastname: Koppenhafer
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Scholz
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D016640:Diabetes, Gestational; D003925:Diabetic Angiopathies / Q000196:embryology*; D005260:Female; D005951:Glucose Tolerance Test; D006128:Growth / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014665:Vasodilator Agents