Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Holemans, K.; Aerts, L.; Assche, F.A. Van

doi:10.1007/bf00500377

Cited by 94 publications

(93 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study maternal diabetes during pregnancy resulted in increased probability in the offspring to develop diabetes without significant insulitis. This effect is not immunologically mediated, but is attributable to intrauterine hyperglycaemia as previously described [15,16]. We observed insulitis predominantly in the progeny of diabetic fathers.…”

Section: Discussionsupporting

confidence: 82%

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

et al. 1993

View full text Add to dashboard Cite

Summary. Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased ~n diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40 % of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90 % of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis and insulin secretion deficiency in CD-1 progeny.

show abstract

Section: Discussionsupporting

confidence: 82%

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

et al. 1993

View full text Add to dashboard Cite

show abstract

“…At 24 wk of age, only females from ad libitum-fed GDM mothers were hyperinsulinemic and had significantly increased body fat compared with females born from WT mothers. Van Assche et al (35,36) found that only adult offspring of moderately diabetic mothers (using streptozotocin) had a deficient ␤-cell response to glucose stimulation, whereas adults from severely diabetic mothers were insulin resistant. When females from these two groups became pregnant, they developed GDM and their fetuses display the same biochemical phenotypes found in the All pups were genotyped at 4 wk of age and the wild-type offspring identified from each litter.…”

Section: Discussionmentioning

confidence: 99%

Effect of Spontaneous Gestational Diabetes on Fetal and Postnatal Hepatic Insulin Resistance in Leprdb/+ Mice

et al. 2003

View full text Add to dashboard Cite

Infant macrosomia is a classic feature of a gestational diabetes mellitus (GDM) pregnancy and is associated with increased risk of adult obesity and type II diabetes mellitus, however mechanisms linking GDM and later disease remain poorly understood. The heterozygous leptin receptor-deficient (Lepr db/ϩ ) mouse develops spontaneous GDM and the fetuses display characteristics similar to infants of GDM mothers. We examined the effects of GDM on maternal insulin resistance, fetal growth, and postnatal development of hepatic insulin resistance. Fetal body weight on d 18 of gestation was 6.5% greater (p Ͻ 0.05) in pups from ad libitum-fed db/ϩ mothers compared with wild-type (WT) controls. Pair-feeding db/ϩ mothers to the intake of WT mothers normalized fetal weight despite less than normal maternal insulin sensitivity. More stringent caloric restriction reduced insulin and glucose levels below WT controls and resulted in fetal intrauterine growth restriction. The level of hepatic insulin receptor protein was decreased by 28% to 31% in both intrauterine growth restriction and fetuses from ad libitum-fed GDM mothers compared with offspring from WT mothers. In 24-wkold adult offspring from GDM mothers, body weight was similar to WT offspring, however, the females from GDM mothers were fatter and hyperinsulinemic compared with offspring from WT mothers. Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. Hepatic glucose-6-phosphatase activity was also inappropriately increased in the adult offspring from GDM mothers. These results suggest that spontaneous GDM in the pregnant Lepr db/ϩ mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus. Abbreviations GDM, gestational diabetes mellitus IGT, impaired glucose tolerance Lepr db/؉ , leptin receptor deficient WT, wild-type IUGR, intrauterine growth retardation IR-␣, insulin receptor ␣ IRS-1, insulin receptor substrate-1 GLUT, glucose transporter PI 3-kinase, phosphotidylinositol-3-kinase Akt (c-PkB), related to A kinase, protein kinase B G-6-Pase, glucose-6-phosphatase HGP, hepatic glucose production Fetal growth and development are primarily determined by the fetal genome, however, the genetic regulation of fetal growth is influenced by different maternal factors, which can exert a stimulatory or an inhibitory effect. Epidemiologic studies have revealed strong statistical links between nutritional experiences during pregnancy and later development of diseases such as obesity and type II diabetes in adulthood (1, 2). Most convincing are the studies in Pima Indians demonstrating that, besides a genetic transmission of diabetes, the...

show abstract

“…Only rats with glucose concentrations exceeding 19.4 mmol/l and insulin concentrations less than < 25 mU/ml were included. It has been shown that glucose concentrations in severe diabetic rats remain consistently high over an extensive time [24]. Control rats (n = 27) were injected with 250 ml of buffer 3 days before mating.…”

Section: Methodsmentioning

confidence: 99%

Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro

et al. 2000

Self Cite

View full text Add to dashboard Cite

The altered metabolic environment in maternal diabetes during pregnancy interferes with normal fetal development. In humans, as well as in rodents, there is an increased incidence of congenital malformations, such as non-closure of the neural folds and deformities of the heart chambers and the skeleton [1,2], possibly induced by high glucose concentrations [3±5], low insulin concentrations [6,7] or ketone bodies [8]. Congenital malformations and fetal growth retardation in humans are found to be induced by the diabetic state as early as the late embryonic period (between the seventh and fourteenth week) [9]. In rodents experimental diabetes impairs, however, the development of the embryo even in the pre-implantation period [10±13]. By a precise metabolic control of diabetes during the early stage of pregnancy, the increased incidence of congenital malformations can be prevented [14,15]. AbstractAims/hypothesis. To investigate the outgrowth of the ectoplacental cone in diabetic rats in vivo and in vitro. Methods. Female Wistar rats were injected intraperitoneally with streptozotocin (75 mg/kg body weight, n = 15), or with control buffer (n = 27) 3 days before mating. On day 9 (day 1 = copulation plug) decidual swellings were weighed and the volume and mitotic index of the embryo and ectoplacental cone were estimated. Also, ectoplacental cones were cultured either in the presence of decidual cells from pseudopregnant diabetic rats or in high glucose concentration media. Cultures were evaluated by the daily outgrowth and by the proportion of giant cells and proliferating cells on day 5.

show abstract

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Cited by 94 publications

References 25 publications

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

Effect of Spontaneous Gestational Diabetes on Fetal and Postnatal Hepatic Insulin Resistance in Leprdb/+ Mice

Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro

Contact Info

Product

Resources

About