Segar Emily M, Norris Andrew W, Yao Jian-Rong, Hu Shanming, Koppenhafer Stacia L, Roghair Robert D, Segar Jeffrey L, Scholz Thomas D
Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Clin Sci (Lond). 2009 Jul 2;117(3):129-38. doi: 10.1042/CS20080550.
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.
糖尿病母亲的后代（ODM）患代谢和心血管功能障碍的风险增加；然而，很少有研究关注孕期患糖尿病母亲的后代对疾病的易感性。我们建立了一个妊娠晚期糖尿病妊娠的动物模型，并对其后代的代谢和血管功能进行了表征。在妊娠第13天，通过腹腔注射链脲佐菌素（50mg/kg体重）诱导怀孕大鼠患糖尿病，并通过每日两次注射胰岛素进行部分控制。在2个月大时，ODM的糖耐量略优于对照组（P<0.05）；然而，到6个月大时，这种趋势发生了逆转。正常血糖-高胰岛素钳夹试验显示雄性ODM存在胰岛素抵抗（P<0.05）。在6-8个月大的雌性ODM中，主动脉对氯化钾、内皮素-1（ET-1）和去甲肾上腺素（NA）的收缩反应显著增强。联合使用L-NNA（NG-硝基-L-精氨酸）时，对ET-1和NA的反应没有明显差异。雌性ODM对乙酰胆碱（ACh）的舒张反应显著受损，但对硝普钠（SNP）的反应未受损。相比之下，雄性对血管收缩剂的反应在组间没有差异，而ODM对SNP和ACh的舒张反应比对照动物更大。因此，孕期糖尿病的发生会导致成年后代出现性别特异性的胰岛素抵抗和血管功能障碍。
