Increased incidence of hepatic insulin-sensitizing substance (HISS)-dependent insulin resistance in female rats prenatally exposed to ethanol

2005 ◽  
Vol 83 (4) ◽  
pp. 383-387 ◽  
Author(s):  
Parissa Sadri ◽  
Dallas J Legare ◽  
Shinichiro Takayama ◽  
W Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Adult Female ◽  
Adult Male ◽  
Female Offspring ◽  
In Utero ◽  
Ethanol Exposure ◽  
Prenatally Exposed ◽  
Fetal Alcohol ◽  
Rat Offspring

Insulin causes the release of the hepatic insulin-sensitizing substance (HISS) from the liver. Hepatic parasympathetic nerves play a permissive role in the release of HISS. HISS-dependent insulin resistance (HDIR) occurs in the absence of HISS. Fetal ethanol exposure has been shown to cause dose-dependent HDIR in adult male rat offspring. Since female offspring are more severely affected by in utero ethanol toxicity, we hypothesized that fetal alcohol exposure causes higher incidence and more severe HDIR in adult female offspring. Adult female rat offspring prenatally exposed to different concentrations of ethanol (0%, 15%, and 20%) were tested for insulin sensitivity using the rapid insulin sensitivity test (RIST). The RIST index was significantly reduced in the 15% (134.1 ± 16.1 mg/kg) and the 20% (98.7 ± 9.7 mg/kg) group compared with the 0% (220.9 ± 27.6 mg/kg) group. Administration of atropine produced significant additional HDIR in the 15% group (82.9 ± 14.5 mg/kg) but not the 20% group (83.8 ± 20.5 mg/kg) indicating complete HDIR had been produced in this group, contrary to the adult male offspring in a previous study. The results are consistent with the hypothesis that adult-female offspring are more severely affected by in utero ethanol exposure compared with adult-male offspring.Key words: fetal, alcohol, insulin resistance, gender, HISS, teratology, diabetes.

Reversal of cardiomyopathy resulting from prenatal exposure to ethanol

1984 ◽  
Vol 42 ◽  
pp. 716-717
Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie
Keyword(s):  
Prenatal Exposure ◽  
Heart Development ◽  
Membrane Integrity ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Pathological Changes ◽  
Prenatally Exposed ◽  
Inner Mitochondrial Membrane ◽  
Fetal Alcohol ◽  
Newborn Mice

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.

Alterations in Ultrastructure of Skeletal Muscle From Newborn Guinea Pigs Following in Utero Exposure to Ethanol

1985 ◽  
Vol 43 ◽  
pp. 686-687
Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie ◽  
T.B. Cole
Keyword(s):  
Skeletal Muscle ◽  
Guinea Pigs ◽  
Muscle Development ◽  
In Utero ◽  
Ethanol Exposure ◽  
Prenatally Exposed ◽  
Chronic Alcoholic ◽  
Test Kit ◽  
Food And Water Intake ◽  
Post Intubation

Ultrastructural alterations of skeletal muscle have been observed in adult chronic alcoholic patients. However, no such study has been performed on individuals prenatally exposed to ethanol. In order to determine if ethanol exposure in utero in the latter stages of muscle development was deleterious, skeletal muscle was obtained from newborn guinea pigs treated in the following manner. Six Hartly strain pregnant guinea pigs were randomly assigned to either the ethanol or the pair-intubated groups. Twice daily the 3 ethanol-treated animals were intubated with Ensure (Ross Laboratories) liquid diet containing 30% ethanol (6g/Kg pre-pregnant body weight per day) from day 35 of gestation until parturition at day 70±1 day. Serum ethanol levels were determined at 1 hour post-intubation by the Sigma alcohol test kit. For pair-intubation the Ensure diet contained sucrose substituted isocalorically for ethanol. Both food and water intake were monitored.

Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring

2012 ◽  
Vol 303 (11) ◽  
pp. E1373-E1385 ◽  
Author(s):  
Miao Sun ◽  
Manuel Maliqueo ◽  
Anna Benrick ◽  
Julia Johansson ◽  
Ruijin Shao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Adult Female ◽  
Late Pregnancy ◽  
Free Testosterone ◽  
Estrogen Receptor Α ◽  
Female Offspring ◽  
Adipocyte Size ◽  
Nonalcoholic Fatty Liver

Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10–11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.

In vivo insulin signaling through PI3-kinase is impaired in skeletal muscle of adult rat offspring exposed to ethanol in utero

2005 ◽  
Vol 99 (2) ◽  
pp. 528-534 ◽  
Author(s):  
Li Chen ◽  
Xing-Hai Yao ◽  
B. L. G. Nyomba
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
In Utero ◽  
Pi3 Kinase ◽  
Adult Rat ◽  
Rat Offspring ◽  
Significant Difference

It is now known that prenatal ethanol (EtOH) exposure is associated with impaired glucose tolerance and insulin resistance in rat offspring, but the underlying mechanism(s) is not known. To test the hypothesis that in vivo insulin signaling through phosphatidylinositol 3 (PI3)-kinase is reduced in skeletal muscle of adult rat offspring exposed to EtOH in utero, we gave insulin intravenously to these rats and probed steps in the PI3-kinase insulin signaling pathway. After insulin treatment, EtOH-exposed rats had decreased tyrosine phosphorylation of the insulin receptor β-subunit and of insulin receptor substrate-1 (IRS-1), as well as reduced IRS-1-associated PI3-kinase in the gastrocnemius muscle compared with control rats. There was no significant difference in basal or insulin-stimulated Akt activity between EtOH-exposed rats and controls. Insulin-stimulated PKC isoform ζ phosphorylation and membrane association were reduced in EtOH-exposed rats compared with controls. Muscle insulin binding and peptide contents of insulin receptor, IRS-1, p85 subunit of PI3-kinase, Akt/PKB, and atypical PKC isoform ζ were not different between EtOH-exposed rats and controls. Thus insulin resistance in rat offspring exposed to EtOH in utero may be explained, at least in part, by impaired insulin signaling through the PI3-kinase pathway in skeletal muscle.

scholarly journals Maternal Rat Diabetes Mellitus Deleteriously Affects Insulin Sensitivity and Beta-Cell Function in the Offspring

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Abdel-Baset M. Aref ◽  
Osama M. Ahmed ◽  
Lobna A. Ali ◽  
Margit Semmler
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Maternal Diabetes ◽  
Serum Glucose ◽  
Time Intervals ◽  
Rat Offspring ◽  
Normal Rat

This study was designed to assess the effect of maternal diabetes in rats on serum glucose and insulin concentrations, insulin resistance, histological architecture of pancreas and glycogen content in liver of offspring. The pregnant rat females were allocated into two main groups: normal control group and streptozotocin-induced diabetic group. After birth, the surviving offspring were subjected to biochemical and histological examination immediately after delivery and at the end of the 1st and 2nd postnatal weeks. In comparison with the offspring of normal control dams, the fasting serum glucose level of offspring of diabetic mothers was significantly increased at the end of the 1st and 2nd postnatal weeks. Serum insulin level of offspring of diabetic dams was significantly higher at birth and decreased significantly during the following 2 postnatal weeks, while in normal rat offspring, it was significantly increased with progress of time. HOMA Insulin Resistance (HOMA-IR) was significantly increased in the offspring of diabetic dams at birth and after 1 week than in normal rat offspring, while HOMA insulin sensitivity (HOMA-IS) was significantly decreased. HOMA beta-cell function was significantly decreased at all-time intervals in offspring of diabetic dams. At birth, islets of Langerhans as well as beta cells in offspring of diabetic dams were hypertrophied. The cells constituting islets seemed to have a high division rate. However, beta-cells were degenerated during the following 2 post-natal weeks and smaller insulin secreting cells predominated. Vacuolation and necrosis of the islets of Langerhans were also observed throughout the experimental period. The carbohydrate content in liver of offspring of diabetic dams was at all-time intervals lower than that in control. The granule distribution was more random. Overall, the preexisting maternal diabetes leads to glucose intolerance, insulin resistance, and impaired insulin sensitivity andβ-cell function in the offspring at different postnatal periods.

Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure

2007 ◽  
Vol 292 (5) ◽  
pp. R1926-R1933 ◽  
Author(s):  
Xing-Hai Yao ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Adult Female ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Female Offspring ◽  
Female Rat ◽  
Glucose Transporter 4 ◽  
Insulin Resistant ◽  
Rat Offspring

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg−1·day−1 by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCζ in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCζ phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.

Periconceptional ethanol exposure alters the stress axis in adult female but not male rat offspring

Stress ◽  
2019 ◽  
Vol 22 (3) ◽  
pp. 347-357 ◽  
Author(s):  
Danielle J. Burgess ◽  
Emily S. Dorey ◽  
Emelie M. Gardebjer ◽  
Helle Bielefeldt-Ohmann ◽  
Karen M. Moritz ◽  
...  
Keyword(s):  
Adult Female ◽  
Ethanol Exposure ◽  
Stress Axis ◽  
Male Rat ◽  
Rat Offspring

Prenatal programming of adult thyroid function by alcohol and thyroid hormones

2004 ◽  
Vol 287 (2) ◽  
pp. E318-E326 ◽  
Author(s):  
Jennifer Slone Wilcoxon ◽  
Eva E. Redei
Keyword(s):  
Thyroid Function ◽  
Adult Female ◽  
Female Offspring ◽  
Thyroid Stimulating Hormone ◽  
Fetal Alcohol ◽  
Adult Rat ◽  
Maternal Alcohol Consumption ◽  
Physiological Adaptations ◽  
Young Offspring ◽  
Maternal Thyroid

Increasing evidence associates environmental challenges early in life with permanent alterations of physiological functions in adulthood. These changes in fetal environment can trigger physiological adaptations by the fetus, called fetal programming, which may be beneficial before birth but permanently influence the physiology of the organism. In this study, we investigated the potential connection between alcohol-induced decreased maternal thyroid function and the hypothalamic-pituitary-thyroid (HPT) function of adult rat offspring. Plasma 3,5,3′-triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were decreased in alcohol-consuming (E) dams on gestational day 21 compared with ad libitum- (C) and pair-fed (PF) controls. No significant differences were found in HPT function in young offspring (3 wk of age) between diet groups. However, adult fetal alcohol-exposed (FAE) offspring had significantly decreased levels of T3 along with elevated TSH compared with control offspring. T4 administration to the mother did not normalize the hypothyroid state of the adult FAE offspring. Interestingly, administration of T4 to control pregnant dams decreased plasma T3 of the adult female offspring only, whereas T4 together with maternal alcohol consumption or pair-feeding led to decreased TSH and T4 in the adult female offspring. Our results suggest that ethanol consumption and T4 administration alter maternal HPT function, leading to prenatally programmed permanent alterations in the thyroid function of the adult offspring.

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