Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

Emily M Segar; Andrew W Norris; Jian-Rong Yao; Shanming Hu; Stacia L Koppenhafer; Robert D Roghair; Jeffrey L Segar; Thomas D Scholz

doi:10.1042/CS20080550

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Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

Journal article

Peer reviewed

Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

Emily M Segar, Andrew W Norris, Jian-Rong Yao, Shanming Hu, Stacia L Koppenhafer, Robert D Roghair, Jeffrey L Segar and Thomas D Scholz

Clinical science (1979), Vol.117(3), pp.129-138

08/01/2009

DOI: 10.1042/CS20080550

PMCID: PMC2884292

PMID: 19203348

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https://www.ncbi.nlm.nih.gov/pmc/articles/2884292View

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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.

Details

Title: Subtitle: Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats
Creators: Emily M Segar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Andrew W Norris - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Jian-Rong Yao - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Shanming Hu - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Stacia L Koppenhafer - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Robert D Roghair - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Jeffrey L Segar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Thomas D Scholz - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Resource Type: Journal article
Publication Details: Clinical science (1979), Vol.117(3), pp.129-138
DOI: 10.1042/CS20080550
PMID: 19203348
PMCID: PMC2884292
NLM abbreviation: Clin Sci (Lond)
ISSN: 0143-5221
eISSN: 1470-8736
Language: English
Date published: 08/01/2009
Academic Unit: Endocrinology and Diabetes; Cardiology; Stead Family Department of Pediatrics; Hematology/Oncology; Center for Biocatalysis and Bioprocessing; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Biochemistry and Molecular Biology; Urology; Neonatology
Record Identifier: 9984093370802771

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