Diabetes in Pregnancy: Decreased Placental Blood Flow and Disturbed Fetal Development in the Rat

Eriksson, Ulf J.; Jansson, Leif

doi:10.1203/00006450-198408000-00012

Cited by 60 publications

(33 citation statements)

References 32 publications

(47 reference statements)

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“…2,3) Considering the positive correlation of serum RAs levels versus HbA1c together with the negative correlation versus age, there is a possibility that the concentrations of serum RAs may be especially elevated in young and severely (highHbA1c) diabetic patients. This hypothesis has clinical importance, in view of higher incidence of fetal malformation from high-HbA1c expectant mothers and diabetic mellitus model animals [14][15][16][17] and the pivotal role of retinoic acid in normal embryonic development. 18) In addition, higher concentrations of serum RA in such diabetic patients may be an exacerbating factor for diabetic pathogenesis, because it is known that retinoic acid suppresses the differentiation of adipocytes, which may modulate the insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbA1c Values.

Yamakoshi

Fukasawa

Yamauchi

et al. 2002

Biological & Pharmaceutical Bulletin

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The nutritional status of lipid and fatty acids, not only glucose, is modified in diabetes mellitus patients. The concentration of retinol, an essential dietary nutrient for normal growth, reproduction, and vision, is also affected in diabetes. Lower serum concentrations of retinol in patients with insulin-dependent diabetes (IDDM) and in streptozotocin-induced diabetic rats, in which the transport mechanism of retinol from liver to the target site is considered to be impaired, were reported. [1][2][3][4][5] In contrast, patients with non insulin-dependent diabetes (NIDDM) have greater serum retinol concentrations than normal subjects. [6][7][8] Recently, PPARg, a ligand-activated transcription factor and a member of the nuclear hormone receptor superfamily, was found to play a pivotal role in the expression of genes associated with metabolism and transport of glucose and lipids.9) Ligand-induced activation of PPARg/RXR heterodimer leads to differentiation of adipocytes in vitro and in vivo, and increases the insulin sensitivity of diabetic animals and human patients. Therefore, the possibility that 9-cisretinoic acid (9cRA), an endogenous ligand of RXR and one of the metabolites of retinol, might be affected in diabetes mellitus patients and be a factor in the pathological aspects of diabetic mellitus, should be considered. All-trans-retinoic acid (ATRA), another isomer of retinoic acid (RA) and a ligand of another nuclear receptor RAR (retinoic acid receptor), has also been recognized as a potent inhibitor of adipocyte differentiation.10,11) Despite the potential importance of RA isomers, which are active metabolites of retinol, the circulating concentrations of these retinoic acids in diabetics have not been thoroughly studied. In this article, we deal with the concentrations of serum retinoic acid isomers in healthy volunteers and type II diabetes mellitus (T2DM) patients, measured by a sensitive HPLC method, and we present a correlation between serum retinoic acids level and hemoglobin A1c (HbA1c) value, an important index of diabetes, in T2DM patients. MATERIALS AND METHODSChemicals ATRA was synthesized as previously described.12) 9cRA and 13-cis-retinoic acid (13cRA) were purchased from Wako Chemicals (Japan).Methanol, acetonitrile, chloroform, ethanol, 2-propanol, nhexane, ethyl acetate (all of HPLC grade) and ammonium acetate, diethyl ether (both grade S) and glacial acetic acid (analytical grade) were obtained from Wako Chemicals. Water for HPLC was prepared by a Milli-Q-water purification system.Subjects Blood samples were collected from 18 healthy volunteers (average age, 32.8Ϯ7.9; BMI average, 21.2Ϯ1.7) and 13 T2DM patients (average age, 56.7Ϯ15.5; BMI average 22.7Ϯ4.3) before meals. Healthy subjects were kept off high-vitamin A diet during the study. The procedures were in accordance with local ethical standards, and informed consent was obtained from all the subjects. Blood sugar was measured with a glucose sensor after blood collection. Quantitative analysis of HbA1c, total cholesterol, and high-...

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Section: Discussionmentioning

confidence: 99%

Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbA1c Values.

Yamakoshi

Fukasawa

Yamauchi

et al. 2002

Biological & Pharmaceutical Bulletin

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“…Thus, decreased placental blood flow (7)(8)(9) and distorted placental morphology (10) have been found in diabetic rats at the end of pregnancy. In addition, changes in the capacity to transfer different nutrients from mother to fetus have been demonstrated in the chorioallantoic placenta of diabetic animals (11,12).…”

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confidence: 99%

Diabetes in Pregnancy: Uterine Blood Flow and Embryonic Development in the Rat

1995

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The uterine blood flow to individual implantation sites was evaluated in early normal and diabetic rat pregnancy, and related to maternal metabolic state, length of gestation, and embryonic outcome. The aim was to search for a possible coupling between the flow rate and embryonic development. We studied pregnant rats of a malformation-prone Sprague-Dawley strain on gestational d 9, 10, 11, and 12, a time period which roughly corresponds to postconception wk 3-6 in human gestation. The blood flow in the uterus was estimated with the aid of a microsphere technique, and the embryos were evaluated with respect to morphology and uterine position. We found increased blood flow in the uterine and decidual tissue of the pregnant diabetic animals compared with normal pregnant rats on all days studied. The blood perfusion peaked on gestational d 10, both in normal and diabetic pregnancy. The implantations tended to be fewer, whereas the resorption and malformation rates were higher, in the left horn than in the right horn. The blood flow in the uterine and decidual tissues was increased in the left horn in diabetic d 10 tissue, as well as d 12 tissues, thereby suggesting that compromised embryonic development is associated with increased rather than decreased supply of nutrients to the implantation site. These findings are in concert with previous in vitro results suggesting that enhanced oxidative stress due to increased substrate availability is an important factor in diabetic teratogenesis. (Pediatr Res 38: [598][599][600][601][602][603][604][605][606] 1995) Abbreviations MD rats and MD embryos, manifestly diabetic rats, and their offspring N rats and N embryos, normal rats and their offspring

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“…16 Severe maternal hyperglycemia invariably is accompanied by growth retardation of the fetuses, probably because of a reduction in uteroplacental blood flow. 17 Fetal insulin levels were found to be normal 18 or decreased. 14 -16 The use of lower doses of SZ during pregnancy has produced inconsistent results.…”

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confidence: 97%

Is Low-Dose streptozotocin in Rats an Adequate Model for Gestational Diabetes Mellitus?

Caluwaerts¹,

Holemans²,

Bree³

et al. 2003

Journal of the Society for Gynecologic Investigation

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Diabetes in Pregnancy: Decreased Placental Blood Flow and Disturbed Fetal Development in the Rat

Cited by 60 publications

References 32 publications

Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbA1c Values.

Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbA1c Values.

Diabetes in Pregnancy: Uterine Blood Flow and Embryonic Development in the Rat

Is Low-Dose streptozotocin in Rats an Adequate Model for Gestational Diabetes Mellitus?

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