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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

02/11/2009

Pubmed ID

19203348

Pubmed Central ID

PMC2884292

DOI

10.1042/CS20080550

Scopus ID

2-s2.0-70149105947   31 Citations

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.

Author List

Segar EM, Norris AW, Yao JR, Hu S, Koppenhafer SL, Roghair RD, Segar JL, Scholz TD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aorta, 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
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00