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Biomedical subjects

L Aerts

Publications and source records attributed to L Aerts.

At least 19 recordsLinked to original sources
PubMed2005

Animal evidence for the transgenerational development of diabetes mellitus.

The mammalian fetus develops inside the uterus of its mother and is completely dependent on the nutrients supplied by its mother. Disturbances in the maternal metabolism that alter this nutrient supply from mother to fetus can induce structural and functional adaptations during fetal development, with lasting consequences for growth and metabolism of the offspring throughout life. This effect has been investigated, by several research groups, in different experimental models where the maternal metabolism during pregnancy was experimentally manipulated (maternal diabetes and maternal malnutrition) and the effect on the offspring was investigated. The altered maternal/fetal metabolism appears to be associated with a diabetogenic effect in the adult offspring, including gestational diabetes. This diabetic pregnancy in the offspring again induces a diabetogenic effect into the next generation, via adaptations during fetal development. These experimental data in laboratory animals are confirmed by epidemiological studies on infants of mothers suffering from diabetes or malnutrition during pregnancy. It can be concluded that fetal development in an abnormal intra-uterine milieu can induce alterations in the fetal metabolism, with lasting consequences for the glucose tolerance of the offspring in adult life. The most marked effect is the development of gestational diabetes, thereby transmitting the diabetogenic tendency to the next generation again. The concept of fetal origin of adult diabetes therefore is of major significance for public health in the immediate and the far future.

Adult↗
PubMed2003

Lifetime consequences of abnormal fetal pancreatic development.

There is ample evidence that an adverse intrauterine environment has harmful consequences for health in later life. Maternal diabetes and experimentally induced hyperglycaemia result in asymmetric overgrowth, which is associated with an increased insulin secretion and hyperplasia of the insulin-producing B-cells in the fetuses. In adult life, a reduced insulin secretion is found. In contrast, intrauterine growth restriction is associated with low insulin secretion and a delayed development of the insulin-producing B-cells. These perinatal alterations may induce a deficient adaptation of the endocrine pancreas and insulin resistance in later life. Intrauterine growth restriction in human pregnancy is mainly due to a reduced uteroplacental blood flow or to maternal undernutrition or malnutrition. However, intrauterine growth restriction can be present in severe diabetes complicated by vasculopathy and nephropathy. In animal models, intrauterine growth retardation can be obtained through pharmacological (streptozotocin), dietary (semi-starvation, low protein diet) or surgical (intrauterine artery ligation) manipulation of the maternal animal. The endocrine pancreas and more specifically the insulin-producing B-cells play an important role in the adaptation to an adverse intrauterine milieu and the consequences in later life. The long-term consequences of an unfavourable intrauterine environment are of major importance worldwide. Concerted efforts are needed to explore how these long-term effects can be prevented. This review will consist of two parts. In the first part, we discuss the long-term consequences in relation to the development of the fetal endocrine pancreas and fetal growth in the human; in the second part, we focus on animal models with disturbed fetal and pancreatic development and the consequences for later life.

Animals↗
PubMed2003

Intra-uterine transmission of disease.

Fetal development is dependent on maternal supply of fuels and building blocks. Disturbed maternal metabolism or inappropriate maternal nutrition confronts the fetus with an unfavourable intra-uterine milieu. Structural and functional adaptations occur during development and maturation of organs. Consequences of these fetal alterations persist postnatally and may result in metabolic alterations throughout life. Gestational diabetes can occur in these offspring and transmit the effect to the next generation. These alterations in fetal development can be associated with fetal macrosomia (maternal diabetes) or fetal growth-restriction (maternal/fetal malnutrition). The relation between birth weight and later metabolic disease therefore is U-shaped. Adult metabolic condition is thus to a considerable extent programmed in utero, fetal and neonatal weight being symptoms of disturbed fetal development. This concept of intra-uterine programming of disease is illustrated with a review of epidemiological human studies and experimental animal studies.

Adult↗
PubMed2003

Fetal growth restriction and consequences for the offspring in animal models.

OBJECTIVE: In the present review we discuss rat models in which intra-uterine growth restriction is obtained through pharmacological (streptozotocin), dietary (global food restriction, low protein diet), or surgical (uterine artery ligation) manipulation of the maternal animal. METHODS: A MEDLINE search was performed on rat models of intrauterine growth restriction (IUGR), ie, streptozotocin, food restriction, low protein diet, or uterine artery ligation and pregnancy and fetal programming, long-term effects or adult offspring. RESULTS: We address the impact of the different maternal conditions for the fetal and neonatal development. The rat models we concentrate on were all associated with fetal hypoinsulinemia and intrauterine growth restriction. Both fetus and neonate adapt to the altered perinatal environment. Some of these adaptations may predispose the offspring to the development of insulin resistance, cardiovascular disease, obesity, and even overt diabetes in later life. CONCLUSION: The adaptations of the fetal metabolism to the altered intrauterine environment have consequences for the offspring, persisting into adulthood and into the next generation.

Animals↗
PubMed2001

Pancreatic islet transplantation in diabetic pregnant rats prevents acquired malformation of the ventromedial hypothalamic nucleus in their offspring.

Exposure to a diabetic intrauterine environment leads to diabetogenic disturbances throughout later life in rats. This is accompanied by a fetally acquired dysplasia of the ventromedial hypothalamic nucleus (VMN) which is decisively involved in the regulation of metabolism. We investigated whether malformation of the VMN is preventable by normalization of gestational hyperglycaemia. Correction of hyperglycaemia in pregnant streptozotocin-diabetic rats was achieved by pancreatic islet transplantation. The number of neurons in the VMN was significantly reduced in adult offspring of non-treated, sham-transplanted mother rats (P<0.05), but did not differ between offspring of islet-transplanted mother rats and offspring of control mothers. In conclusion, prevention of VMN malformation in offspring of islet-transplanted diabetic mothers might be co-responsible for normalization of their glucose homeostasis during life.

Animals↗
PubMed2001

Long-term consequences for offspring of diabetes during pregnancy.

There is evidence that the diabetic intra-uterine environment has consequences for later life. Maternal diabetes mainly results in asymmetric macrosomia. This macrosomia is associated with an increased insulin secretion and overstimulation of the insulin producing B-cells during fetal life. In later life, a reduced insulin secretion is found. Intra-uterine growth restriction is present in severe maternal diabetes associated with vasculopathy. Intra-uterine growth restriction is associated with low insulin secretion and reduced development of the insulin receptors. In later life, these alterations can induce insulin resistance. The long-term consequences of an abnormal intra-uterine environment are of primary importance world-wide. Concentrated efforts are needed to explore how these long-term effects can be prevented.

Animals↗
PubMed2001

Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation.

Animals↗
PubMed2000

PROLACTIN-deficiency in adult offspring of diabetic mothers.

Maternal diabetes induces fetal alterations, resulting in lasting consequences for the glucose tolerance of the offspring over several generations. In our experimental rat model, circulating prolactin, oestradiol, progesterone and corticosterone levels, known to influence insulin secretion and action, are determined in plasma of female adult offspring of mildly and severely diabetic mothers. Prolactin and progesterone levels are equally low in both groups as compared to controls, stressing the involvement of the CNS in the transgeneration effect; oestradiol and corticosterone levels are normal. No correlation is found between these hormonal alterations and the known differences in glucose tolerance.

Animals↗
PubMed1998

Ultrastructural evaluation of B-cell recruitment in virgin and pregnant offspring of diabetic mothers.

Adult offspring of diabetic rat mothers display a disturbed glucose tolerance and gestational diabetes. The amount of endocrine pancreas and of B-cells is largely sufficient in these non-pregnant and pregnant youngsters. The present work aims a morphometric evaluation of B-cell activity in adult youngsters from control, mildly and severely diabetic mothers, in basal condition and in their adaptation to pregnancy. B-cells are divided, on basis of the ultrastructural morphology of their organelles, in dark non-activated B-cells and pale activated B-cells. These data are related to the concepts of functional B-cell heterogeneity and dose-dependent recruitment of pancreatic B-cells on stimulation. The recruitment of B-cells in each of the groups is evaluated from the proportion pale/dark B-cells. In control animals this is about 50/50, in both experimental groups there is a marked predominance of pale B-cells. During normal pregnancy, a shift occurs towards a majority of pale B-cells. In the offspring of diabetic mothers, the ratio does not further change during gestation. It can be concluded that the disturbance in B-cell stimulation and the development of gestational diabetes in offspring of diabetic mothers is associated with a maximal recruitment of the B-cells already in basal non-pregnant condition.

Animals↗
PubMed1998

Fetal growth and long-term consequences in animal models of growth retardation.

Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein-calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation.

Animals↗
PubMed1998

Fetal growth and consequences for later life.

There is evidence that an abnormal intrauterine environment has consequences for later life. Intrauterine growth retardation is associated with low insulin secretion during fetal life and probably a reduced development of insulin receptors. In later life these alterations can induce insulin resistance. Macrosomia is associated with an increased insulin secretion during fetal life and exhaustion of the insulin producing B cells. In later life a reduced insulin secretion is found. The working mechanisms have been explored in experimental studies. Normalisation of the diabetic intrauterine milieu can prevent consequences in later life. There are also indications that vascular changes in later life can be reduced by anti-oxidantia. In the human intrauterine growth retardation is related in later life with insulin resistance, vascular diseases and preeclampsia; macrosomia is related with gestational diabetes and breastcarcinoma.

Animals↗
PubMed1997

The endocrine pancreas in virgin and pregnant offspring of diabetic pregnant rats.

Diabetes of the mother during pregnancy induces structural and functional adaptations in the fetal endocrine pancreas. We have previously shown in our experimental rat model, that the impact of this abnormal intra-uterine milieu leads, in the adult offspring, to a disturbance of the glucose homeostasis and to the development of gestational diabetes. The aim of the present work is to investigate wether these functional differences can be explained by structural differences at the level of the endocrine pancreas. Therefore the size and the structure of the endocrine pancreas, as well as the contribution of the insulin-, glucagon-, somatostatin- and PP-cells, were investigated morphometrically in the adult youngsters of mildly and of severely diabetic mothers, since both display a disturbed glucose tolerance but with divergent characteristics. Also the adaptation of their endocrine pancreas to pregnancy was measured and compared to that of a control pregnancy. In the offspring of mildly diabetic mothers, the size of the endocrine pancreas and the distribution of the islets of Langerhans are normal. Also the doubling of the endocrine mass during pregnancy is similar to controls. The high proportion of A-cells, especially in relation to a normal B-cell mass and the low amount of PP-cells, might play a role in the impairment of the insulin response in these animals and in the development of gestational diabetes. In the offspring of severely diabetic mothers a clear hypertrophy of the endocrine pancreas is noted, which is mainly due to the presence of numerous small islets and which does not increase further during pregnancy. In these animals, the size of the endocrine pancreas and of the B-cell mass have reached 'pregnant' values without pregnancy, which coincides with an exaggerated insulin output and peripheral insulin resistance, as during normal pregnancy. No further increase in islet mass is seen during pregnancy, which is associated with gestational diabetes.

Animals↗
PubMed1994

The endocrine pancreas in nonimmune hydrops fetalis.

OBJECTIVE: Our purpose was to compare the endocrine pancreas of hydropic infants of immune and nonimmune origin. STUDY DESIGN: A quantitative morphologic study was performed on the pancreas in 10 infants with immune and nonimmune hydrops. The volume density of the endocrine pancreas in the gland was calculated, as was the numerical density of the endocrine cells in the islets. The percentage of the different cell types was measured on immunohistochemical stained slides. Ten normal infants were used as controls. RESULTS: An increased amount of endocrine tissue and an increased total number of islet cells of immune and nonimmune origin is present in hydropic infants. However, an increased proportion of the insulin-producing B cells is not present. CONCLUSIONS: The endocrine pancreas in hydrops fetalis of immune and nonimmune origin is equal, excluding hemolysis as the stimulating factor for equilibrated islet overgrowth. Metabolic stimuli, as seen in infants of diabetic mothers, are probably not involved, because they preferentially stimulate the insulin-producing B cells.

Case-Control Studies↗
PubMed1993

In vivo glucose utilization by individual tissues in virgin and pregnant offspring of severely diabetic rats.

Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver and extrahepatic tissues; this insulin resistance does not worsen during pregnancy. In this study, we determined the glucose metabolic index in tissues of anesthetized virgin and pregnant control and SDF rats in basal conditions and during a euglycemic hyperinsulinemic clamp. Tissues comprised insulin-sensitive tissues (five skeletal muscles, diaphragm, and periovarian white adipose tissue) and control tissues (duodenum and cerebrum). In addition, this study measured the GMI of placenta and fetuses. In basal conditions, SDF rats showed a slight decrease (9-29%) in the GMI of skeletal muscles compared with control rats; it was not altered by pregnancy in any of the tissues. During physiological hyperinsulinemia, virgin SDF rats exhibited a 25-70% decrease in the GMI of skeletal muscles compared with control rats; this decrease was not observed in diaphragm, or in adipose tissue in which the GMI was found to be increased. During pregnancy, SDF rats did not show an additional drop in the GMI of skeletal muscles, whereas the GMI of both skeletal muscles and adipose tissue was clearly diminished (25-60%) in control rats. The GMI of skeletal muscles was therefore comparable in pregnant control rats and SDF rats. The placental, but not fetal, GMI was increased by 24% during hyperinsulinemia in control rats; the placental and fetal GMIs, in basal and hyperinsulinemic conditions, were similar in control rats and SDF rats. In conclusion, skeletal muscles, but not white adipose tissue, are involved in the peripheral insulin resistance of the SDF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Islet transplantation in diabetic pregnant rats normalizes glucose homeostasis in their offspring.

Diabetes of the mother during pregnancy induces alterations in the fetus, resulting in impaired glucose homeostasis in the offspring. In youngsters of severely diabetic mothers, during glucose infusion, hyperinsulinemia is associated with hyperresponsiveness of the beta-cells and insulin resistance. In order to normalize maternal metabolism, isolated islets from neonatal rats were transplanted into the vena porta of severely hyperglycemic (Streptozotocin) rats at day 15 of gestation. Strict glycemic control of the mothers was achieved throughout further gestation and lactation. In the adult offspring of these transplanted rats insulin levels during glucose infusion were significantly lower than in the offspring of sham-transplanted diabetic mothers and were not different from controls. The work confirms that the diabetic state of the mother during late gestation (the period of development of the endocrine pancreas and of the insulin-receptor system) is the inducing factor for the abnormal glucose homeostasis in the offspring, and normalisation of the hyperglycemia eliminates these long-term consequences.

Analysis of Variance↗
PubMed1991

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

Our previous work has suggested the presence of an insulin resistance in the adult offspring of streptozotocin-diabetic pregnant rats. In this study we used the euglycaemic hyperinsulinaemic clamp technique with an isotope-dilution method to define and quantify this postulated insulin resistance in adult offspring of streptozotocin-diabetic rats. Under basal conditions, these rats had a lower body weight than control rats, but their glucose and insulin concentrations were normal. During the hyperinsulinaemic clamp, the steady-state glucose infusion rate was significantly lower in the offspring of streptozotocin-diabetic rats than in both age- and weight-matched controls, indicating insulin resistance. Basal peripheral tissue glucose utilization was normal in the offspring of streptozotocin-diabetic rats, but the dose-response curve was shifted to the right:insulin concentrations causing half-maximal stimulation of glucose utilization were increased by about 60% in the offspring of diabetic rats; the maximal stimulation of glucose utilization, however, was unaltered. Basal hepatic glucose production was normal, but again, half-maximal suppression of glucose production occurred at insulin concentrations 50% higher than in control rats; in addition, the maximal suppression of glucose production was significantly decreased, even at insulin concentrations of 5700 microU/ml. These data are evidence for an insulin resistance in the adult offspring of streptozotocin-diabetic rats, characterized by: (1) a decreased insulin sensitivity by peripheral glucose-utilizing tissues, and, (2) a decreased sensitivity and responsiveness of the liver.

Animals↗