J. J. Hoet

Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas.

The administration of a low protein (LP, 8% protein/dry matter) but isocaloric diet to gestating rats did not affect their fertility, but slightly reduced the quantity of food intake as well as body weight gain. The LP diet also did not affect the placental weight, but the weight of the offspring was decreased. Accordingly the fetal endocrine pancreas was altered by the LP diet. Two different morphometric analyses showed that in the LP neonate B-cell proliferation and islet size were reduced in the head of the pancreas. In the pancreatic tail, these parameters were also decreased but to a lesser extend. Islet vascularization in the neonates was dramatically reduced in both parts of the pancreas when the mothers were fed with the LP diet.

Islet Function in Offspring of Mothers on Low-Protein Diet During Gestation

A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.

Nutritional influences on pancreatic development and potential links with non-insulin-dependent diabetes.

Diabetes is widespread throughout the world and affects young children as well as adults, male and female alike. The prevalence of diabetes may be 3-5% in the Western hemisphere but may reach 50% in specific populations like the Nauruans or the Pima Indians and 15-20% in Hispanics and Afro-Americans. It is associated with major complications such as blindness, renal insufficiency and cardiovascular diseases including hypertension and myocardial infarction. Diabetes afflicts the less privileged and deprived in a society (King & Rewers, 1993). Immigrants and specific populations such as Ethiopian Jews immigrating to Israel also have a high prevalence (Cohen et al. 1988). The disease and its complications run in families, often on the mother’s side (Liao et al. 1993; Mitchell et al. 1993). Impaired glucose tolerance is strikingly more common in women than men. Between 21 and 39 years of age, 11-20% of many populations worldwide may be afflicted by impaired glucose tolerance. In some populations, such as female Muslim Asian Indians it may reach 32% (King & Rewers, 1993). Population studies have indicated that progeny weighing less than 2.5 kg at birth and 8 kg at 1 year are afflicted with diabetes and cardiovascular diseases in more than 45% of the individuals reaching the age of 64 years (Hales et al. 1991). Recent data indicate also that young children born in underprivileged areas where low birth weight is endemic have high cholesterol and blood sugar levels, as well as abnormal insulin levels and hypertension (King et al. 1990). These abnormal biological features are not an acquisition of adult age because they may be present already at 3 years of age (The Bogalusa Heart Study, 1987). The yardstick frequently used to evaluate mothers’ health and its influence on the neonate is to record birthweight and other fetal variables which have been correlated with later degenerative diseases in the progeny (Barker, 1992). The foregoing implies that the metabolic and vascular anomalies leading to chronic ailments such as diabetes, hypertension and cardiovascular diseases originate early in life and are initiated, in all likelihood, in utero. The issue remains why a greater prevalence of

Influences of pre- and postnatal nutritional exposures on vascular/endocrine systems in animals.

Human epidemiological and animal studies have revealed the long-term effects of malnutrition during gestation and early life on the health of the offspring. The aim of the current review is to survey the different means of achieving fetal malnutrition and its consequences, mainly in animals, and to identify key areas in which to direct future research. We address the impact of various models of a maternal protein-restricted diet and global maternal caloric restriction (either through the reduction of nutrient supply or through mechanic devices), the influence of maternal diabetes, and other maternal causes of fetal damage (maternal infections and toxic food components). More specifically, we enumerate data on how the different insults at different prenatal and early postnatal periods affect and program the development and the function of organs involved in diabetes, hypertension, and cardiovascular disease. Particular emphasis is given to the endocrine pancreas, but insulin-sensitive tissues, kidneys, and vasculature are also analyzed. Where available, the protective effects of maternal food supplementation for fetal organ development and function are discussed. Specific attention is paid to the amino acids profile, and the preventive role of taurine is discussed. Tentative indications about critical time windows for fetal development under different deleterious conditions are presented whenever possible. We also discuss future research and intervention.

Localization of high-affinity GABA uptake and GABA content in the rat duodenum during development.

SummaryThe localization of high-affinity uptake sites for 3Hγ-aminobutyric acid (3H-GABA) was investigated in the rat duodenum during ontogenesis and also at the adult stage (from 15.5 days of fetal life up to 105 days post natum) by means of low- and high-resolution autoradiography. At all stages studied, specific endocrine cell types of the epithelium were labelled and an intense uptake was detected in the nervous tissue, especially in glial cells but also in scarce neurones. When the incubation medium was supplemented with β-alanine (1 mM), a blocker of the glial uptake for GABA, the labelling persisted only in endocrine cells and in few neurones. The intensity and the frequency of the labelling decreased at later periods compared to the earlier developmental stages. The GABA content of the duodenum as measured by a new ion-exchange column chromatography-HPLC-coupled method was higher in the early postnatal period compared to later stages. These observations suggest that GABA, in addition to being a neurotransmitter, may play an important role during development of the duodenum.

Is Gestational Diabetes a Clinical Entity

SummaryGestational diabetes is a clinical entity associated with a significant incidence in diabetes in the later life of the mother and increase in fetal and neonatal morbidity. Lack of agreement on diagnostic criteria and the methodology of glucose tolerance testing has led to inconsistency in the results of published studies. It is recommended that all women should be screened for carbohydrate intolerance in pregnancy.

Slowly exchangeable pool of estradiol in the rat uterus

Abstract Chase experiments, alternating infusions with 14C and 3H labelled estradiol, were performed in adult rats. After infusion, purified nuclei were extracted from uterine homogenates and the 3H/14C ratio was determined in cytosol and nuclear fractions. It was shown that {414C}estradiol exchanged progressively with {6,73H}estradiol in all subcellular fractions, but at a much slower rate than in the plasma. The retardation was more evident in the Tris-EDTA-KCl extract (SIII) of the nuclear preparations than in other soluble “receptors” from the cyctosol (SI) or the particulate fraction (SII). The final residual precipitate of the nuclear fraction contained a limited pool of estradiol, more slowly exchangeable than in other fractions. These data confirm the extensive recycling of estradiol within the uterine cell. They also show in the nucleus, the existence of a more slowly exchangeable pool, of limited capacity, which appears to be possibly a final but still reversible step in the hormone distribution within the cell. The implication of this limited pool in the hormonal activity is briefly discussed.

Localization of Gaba High-affinity Binding-sites in the Pancreas of Neonatal Rat

SummaryThe localization of gamma-aminobutyric acid (GABA) high-affinity binding sites was investigated in the exocrine and endocrine pancreas of neonatal rats by means of 3H-GABA autoradiography. GABA-binding was identified on Schwann cells and on the cells of the intralobular excretory ducts. In the endocrine part of the pancreas, no labelling was observed except in peripheral islet cells which, on the basis of their scarcity and distribution, could be somatostatin cells. Furthermore, peri-insular innervation showed considerable labelling.

Fetal plasma prolactin levels and fetal growth in relation to maternal CB-154 treatment in the rat.

Pregnant Wistar rats received daily injections of 1 mg of CB-154 starting Day 14 of gestation. The CB-154 treatment did not suppress maternal plasma prolactin levels, but a significant decrease in fetal prolactin was seen. This suppression of prolactin levels in fetal plasma however did not influence fetal growth. These results do indicate that prolactin does not act as a growth promoting hormone in fetal rats.

The pattern of plasma insulin response to glucose in patients with a previous myocardial infarction. The respective effects of age and disease.

Plasma insulin and blood sugar variations were investigated during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in 10 patients aged 32 to 41 and 10 Patients aged 48 to 60 who had suffered a myocardial infarction at least three months previously. The results obtained in each group of patients were compared with those of ten normal subjects of corresponding age. The respective influences of age and cardio‐vascular disease on the pattern of the plasma insulin and blood sugar responses to the glucose load were dissociated on the basis of analysis of variance.—Advancing age was associated with a rise in the mean blood sugar level during OGTT and a lowering of the glucose assimilation coefficient during IVGTT, but it was not accompanied by a significant change in the plasma insulin levels during either of the two tests.—Cardiovascular disease was associated with an augmentation of the mean blood sugar level during OGTT, but also with a prolonged and excessive response in plasma insulin. During IVGTT the glucose assimilation coefficient and the plasma insulin variations were not statistically different in the patients with a previous myocardial infarction and in the normal subjects.—The previous occurrence of a myocardial infarction is thus associated with a hyperinsulinism during OGTT, but not after a rapid stimulation as realized during IVGTT. The nature of the gastrointestinal factors involved in the genesis of this hyperinsulinism remains a matter of conjecture.