Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats. Clin Sci (Lond) 2009 Jul 02;117(3):129-38
Date
02/11/2009Pubmed ID
19203348Pubmed Central ID
PMC2884292DOI
10.1042/CS20080550Scopus ID
2-s2.0-70149105947 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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.
Author List
Segar EM, Norris AW, Yao JR, Hu S, Koppenhafer SL, Roghair RD, Segar JL, Scholz TDAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAorta, Abdominal
Birth Weight
Blood Glucose
Diabetes Mellitus, Experimental
Diabetes, Gestational
Diabetic Angiopathies
Female
Glucose Tolerance Test
Growth
Insulin
Insulin Resistance
Male
Muscle Contraction
Muscle, Smooth, Vascular
Pregnancy
Rats
Rats, Sprague-Dawley
Vasodilation
Vasodilator Agents
