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Biomedical subjects

J J Hoet

Publications and source records attributed to J J Hoet.

At least 19 recordsLinked to original sources
PubMed2001

Islet cryopreservation: improved recovery following taurine pretreatment.

Simple and efficient freezing methods with maximal postthawing recovery form the basis of ideal cryopreservation. Taurine (2-amino ethanesulfonic acid), an end-product of sulphur amino acid metabolism, is one of the most abundant free amino acids in the body. The membrane stabilizing, free radical scavenging, and osmoregulatory roles of taurine have been well documented. We studied the effect of physiological and supra-physiological concentrations (0.3 and 3.0 mM) of taurine on islet cryopreservation. Islet viability on cryopreservation was significantly improved in both the taurine-treated groups (91.9 +/- 2.3% in 0.3 mM and 94.6 +/- 1.58% in 3.0 mM group, p < 0.05) compared with the controls (85.7 +/- 3.4%). Loss of peripheral islet cells was highly reduced in the taurine group, as examined under phase contrast and quantified by islet morphometric analysis (p < 0.05) using a digital image analysis system. Taurine-treated islets showed significant reduction in lipid peroxidation (0.905 and 0.848 nM MDA/microg protein for 0.3 and 3.0 mM taurine, respectively, p < 0.05) compared with control (1.307 nM MDA/microg protein) islets. In all, 500 islet equivalents (IE) of treated or control group islets were transplanted to BALB/c mice rendered diabetic with STZ. All animals showed a normal glucose clearance following a glucose load. Graft functionality was confirmed by normoglycemia (fasting plasma glucose: fpg < 150 mg/dl) after transplantation and reappearing hyperglycemia (fpg > 200 mg/dl) following removal of the graft. Suboptimal islet transplantation using 250 IE suggests that the grafted islet mass was inadequate for diabetes reversal. In addition, no significant differences were observed in the islet insulin content between the three groups following cryopreservation of the islets at -196 degrees C. Our studies indicate that taurine pretreatment and its continued presence during islet cryopreservation improves the postthawing viable recovery of islets.

Animals↗
PubMed2000

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.

Animals↗
PubMed1999

Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development.

Experimental investigations in animals have highlighted the role of early reduced calorie and protein nutrition on fetal cardiovascular development, and the occurrence of a transition from a low fetal arterial blood pressure in late gestation to a high arterial blood pressure postnatally. These observations may explain the correlation between health, including appropriate nutrition, in pregnant women and the outcome of their pregnancies. Emphasis has been placed on low birth weight infants who have an increased risk of developing cardiovascular diseases, including hypertension, coronary heart disease and stroke in adulthood. Vascular pathology in adults is not always associated with low birth weight and animal experiments indicate that substantial changes in cardiovascular and endocrine function can result from maternal or fetal undernutrition without impairing fetal growth. Experimental investigation on organogenesis shows the pivotal role of adequate protein availability as well as total caloric intake. Amino acid metabolism in the feto-maternal unit appears to have a key influence on the development of organs involved in chronic degenerative disease in the adult. Experimental investigation has also highlighted the role of carbohydrate metabolism and its effect on the fetus in this respect. Either restriction of protein intake or diabetes in pregnant rats has intergenerational effects at least on the endocrine pancreas and the brain. Further investigation is needed to clarify the mechanisms involved and lead to a new understanding of the importance of nutrition during pregnancy. This will provide an important approach to the primary prevention of diabetes and chronic degenerative diseases.

Animal Nutritional Physiological Phenomena↗
PubMed1999

A low-protein isocaloric diet during gestation affects brain development and alters permanently cerebral cortex blood vessels in rat offspring.

In humans, low birth weight is associated with nonfatal stroke, cardiovascular disease and diabetes at adulthood. The aim of this study was to investigate in rats the effect of early protein restriction, inducing low birth weight, on brain and endocrine pancreas vascularization at birth and to study if such alterations lasted until adulthood. Pregnant rats were fed either 20 or 8% protein isocaloric diets. Control newborns were nursed by their dams fed the 20% protein diet and low protein (LP) pups by dams fed either the 8 or 20% protein diet. The diets given during lactation were maintained until adulthood. The blood vessel density of cerebral cortex analyzed by morphometry in 3-d-old pups from dams fed the 8% protein diet was lower than in control (C). It remained lower at adulthood whether a LP or a C diet was given postnatally. Reduction of vascularization at adulthood induced by the LP diet limited to fetal life seems characteristic for the brain since vascularization of islets of Langerhans was reduced in neonates but normalized at adulthood by a C diet postnatally. Body and brain weights were lower in LP pups and adults. DNA concentration was lower in forebrain and higher in cerebellum in LP pups. In brain of LP adults, DNA, protein, cholesterol and phospholipid concentrations were lower and were restored at adulthood by a normal diet after birth. In conclusion, cerebral cortex of offspring exposed to a LP isocaloric diet during fetal development showed reduced vascularization which remained throughout life.

Analysis of Variance↗
PubMed1999

A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II.

A programmed turnover of pancreatic beta cells occurs in the neonatal rat involving a loss of beta cells by apoptosis, and their replacement by islet cell replication and neogenesis. The timing of apoptosis is associated with a loss of expression of a survival factor, insulin-like growth factor-II (IGF-II), in the pancreatic islets. Offspring from rats chronically fed a low protein isocalorific diet (LP) exhibit a reduced pancreatic beta cell mass at birth and a reduced insulin secretion in later life. This study therefore investigated the impact of LP on islet cell ontogeny in the late fetal and neonatal rat, and any associated changes in the presence of IGFs and their binding proteins (IGFBPs). Pregnant Wistar rats were fed either LP (8% protein) or normal (C) (20% protein) chow from shortly after conception until the offspring were 21 days postnatal (PN). Bromo-deoxyuridine (BrdU) was administered 1 h before rats were killed and pancreata removed from animals between 19.5 days fetal life and postnatal day 21. Offspring of rats given LP diet had reduced birthweight, pancreatic beta cell mass, and pancreas insulin content, with smaller islets compared with control fed animals, which persisted to weaning. Histological analysis showed that islets from pups given LP diet had a lower nuclear labeling index with BrdU in the beta cells, although, paradoxically, more beta cells showed immunoreactivity for proliferating cell nuclear antigen (PCNA). Because PCNA is present in G1 as well as S phase of the cell cycle, we quantified the number of beta cells immunopositive for cyclin D1, a marker of G1, and NEK2, an indicator of cells in G2 and mitosis. More beta cells in islets from LP-fed animals contained cyclin D1, but less contained NEK2 than did those in controls. This suggests that the beta cell cycle may have a prolonged G1 phase in LP-fed animals in vivo. Offspring of rats given C diet had a low rate of islet cell apoptosis detected by the TUNEL method in fetal and neonatal life (1-2%), with a transient increase to 8% at PN day 14. Offspring of rats receiving LP diet demonstrated a significantly greater level of islet cell apoptosis at every age, rising to 15% at PN 14. IGF-II mRNA was quantified in whole pancreas and was significantly reduced in LP-fed animals at ages up to PN day 10. IGF-II immunoreactivity within the islets of LP-fed rats was also less apparent, but no changes were seen in immunoreactive IGF-I or IGFBPs-2 to -5. These findings show that LP diet changes the balance of beta cell replication and apoptosis in fetal and neonatal neonatal life, which may involve an altered length of beta cell cycle, and contribute to the smaller islet size and impaired insulin release seen in later life. A reduced pancreatic expression of IGF-II may contribute to the lower beta cell proliferation rate and increased apoptosis seen in the fetus and neonate after feeding LP diet.

Animals↗
PubMed1998

Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet.

An isocaloric low-protein (LP) diet (8% instead of 20% in controls) given to dams during gestation reduces the fractional insulin release of stimulated fetal islets. The LP diet lowers the plasma concentration of taurine in both pregnant rats and their fetuses. This study reports the effect of taurine on the in vitro release of insulin from control and LP fetal islets. Direct stimulation with taurine, methionine or leucine increased the release of insulin from control islets. Nevertheless, no effect on LP islets was observed with either taurine or methionine. The release of insulin from LP islets was reduced with leucine. The in vitro addition of taurine (0. 3 or 3 mM) to the culture medium increased the release of insulin from the control islets in response to arginine or leucine, but it did not restore the reduced responsiveness of LP islets to these amino acids. When 2.5% taurine was added to the drinking water of control or LP dams (groups C+T and LP+T) throughout gestation, the concentration of taurine increased in the serum of dams and fetuses of both groups. The release of insulin from the LP+T fetuses was restored to control levels when stimulated with taurine, methionine, leucine or arginine. In conclusion, taurine stimulated control fetal islets in vitro, but failed to do so in LP islets. However, the addition of taurine to the diet of LP dams restored to normal the release of insulin from LP fetal islets, indicating the importance of taurine during development for a normal fetal beta cell function.

Analysis of Variance↗
PubMed1997

Changes of islet size and islet size distribution resulting from protein-malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Bodyweight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (< or = 100 microns2) and a decrease in the population of large islets (> 20,000 microns2). In lean and obese rats fed low protein, beta-cell weight was significantly lower, beta cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancrease in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.

Animals↗
PubMed1996

Nutrient metabolism in pancreatic islets from protein malnourished rats.

The metabolism of D-[5-3H]glucose, D-[3,4-14C]glucose, [2-3H]glycerol, L-[U-14C]glutamine, L-[1-14C]-leucine, and L-[U-14C]leucine was investigated in pancreatic islets isolated from either control rats or animals fed a low-protein isocaloric diet, containing 8% instead of 20% protein, during both fetal and postnatal life. In the latter animals, decreases in body weight, plasma insulin concentration, and insulinogenic index were associated with two major anomalies of islet nutrient metabolism. First, an imbalance between oxidative and anaerobic glycolysis was found in the islets of rats fed the low-protein isocaloric diet. It coincided with a decreased circulation in the glycerol phosphate shuttle, as judged by the generation of 3HOH from [2-3H]glycerol, and was probably attributable to the deficiency of mitochondrial FAD-linked glycerophosphate dehydrogenase previously documented in islet homogenates of the rats fed low protein. Second, the transamination of L-leucine to 2-ketoisocaproate was decreased in the low-protein-fed rats, while the oxidative decarboxylation of the 2-keto acid and the further catabolism of isovaleryl CoA occurred at normal rates when expressed relative to the initial transamination rate. These metabolic anomalies may account, in part at least, for the impairment of insulin release in protein malnutrition.

Acyl Coenzyme A↗
PubMed1996

Pre- and postnatal low protein diet affect pancreatic islet blood flow and insulin release in adult rats.

The pancreatic islet blood flow and insulin secretion of adult rats submitted to an isocaloric low protein diet (8% vs. 20%) during pre- and postnatal life were investigated by the nonradioactive microsphere technique. In the basal state, female rats chronically exposed to a low protein diet (LP) displayed a specific marked decrease in islet blood flow (10 +/- 2 vs. 29 +/- 5 microliters/min.g pancreas; P < 0.01) and overall pancreatic blood flow (P < 0.01). The plasma insulin level, however, was not affected. During a glucose challenge, the control animals enhanced their islet blood flow 2.3-fold, whereas the LP group reached control values with a 6-fold increase. Plasma insulin levels rose similarly in the control and LP animals. A third group of animals designated the recuperation group, exposed to a low protein diet only in utero, displayed islet blood flow comparable to control values, but increased basal plasma insulin (2.0 +/- 0.3 vs. 1.2 +/- 0.1 ng/ml; P < 0.05). These data are consistent with the possibility of dissociation of islet blood flow and insulin release under basal conditions, which may not be the case after a glucose challenge. Furthermore, the low blood flow values in the LP group may reflect an adaptive physiological response, an impaired pancreatic vasculogenesis, or a dysfunction of endothelial cells.

Aging↗
PubMed1996

Stimulatory effects of taurine on insulin secretion by fetal rat islets cultured in vitro.

Islets of rat fetuses born to mothers fed a low protein diet (LP) have a depressed insulin secretion in vitro in response to secretagogues. These fetuses have lower plasma levels of taurine than controls. The aim of this study was to analyze the effect of taurine on fetal islets insulin secretion. After 5 days of culture in serum containing standard RPMI medium, islets were cultured for 2 days in serum-free DME/F12 medium with 8.2 or 16.7 mM glucose alone or with taurine at 0.3 or 3 mM. They were then incubated for 120 min in Krebs Ringer solution with glucose alone (5.6 or 16.7 mM) or glucose (5.6 mM) added to leucine or arginine (both at 10 mM). In both concentrations of glucose, taurine increased the fractional insulin release by islets stimulated with secretagogues tested during the incubation. The effect did not seem to be mediated by changes in cAMP content. In a second set of experiments, islets cultured in RPMI medium for 7 days were incubated in the presence of Krebs Ringer solution with leucine (10 mM) or with sulfur amino acids (taurine at 10 mM, methionine or cysteine at 5 mM) for 120 min. Taurine and methionine stimulated insulin release at the same magnitude as leucine, whereas cysteine had no effect. In conclusion, taurine enhances insulin secretion by fetal islets, at least in vitro. Low taurine levels in fetuses from LP mothers might be implicated in their depressed insulin secretion.

Animals↗
PubMed1995

Impaired activity of rat pancreatic islet mitochondrial glycerophosphate dehydrogenase in protein malnutrition.

In rats that received a low protein isocaloric diet (protein content of the diet: 8 instead of 20%) during fetal life and thereafter up to the time of sacrifice at 12-13 weeks of age, a low plasma insulin concentration, a decreased insulin content of isolated pancreatic islets, and an impaired secretory response of the islets to either D-glucose or the association of L-leucine and L-glutamine coincided, in islet homogenates, with a low activity of the mitochondrial glycerophosphate dehydrogenase and an abnormally high ratio between glutamate-alanine and glutamate-aspartate transaminase activities. Opposite enzymatic changes were found in liver extracts of the same rats. No obvious change in these hormonal, secretory, and enzymatic variables were observed when the period of protein deficiency was restricted to fetal life. These findings support the view that, in protein malnutrition, an impaired activity of pancreatic B-cell mitochondrial glycerophosphate dehydrogenase contributes, possibly in association with other enzymatic anomalies, to the perturbation of islet function.

Animals↗
PubMed1994

Prevention of the cytotoxic effect of IL-1 by human lysozyme on isolated rat islets.

Macrophages are present in the initial phase of the autoimmune process involved in the destruction of the endocrine pancreas in IDDM via the secretion of cytokines such as IL-1 beta. Macrophages also secrete lysozyme. Besides its action on the bacterial cell wall, lysozyme has an important physiological and immunological role. Human lysozyme is an in-situ modulator of the inflammatory reactions. We investigate the protective role of human lysozyme in vitro against the cytotoxic effect of IL-1 beta or of IL-1 beta combined with IFN-gamma on isolated rat islets. Precultured newborn rat islets were incubated with human or chicken lysozyme (50.000 U/ml) over 3 days. Human IL-1 beta (100 U/ml) or IL-1 beta (5 U/ml) + INF-gamma (100 U/ml) was added for the last 2 days and tritiated thymidine for the last 24 hrs. In another set of experiments, islets were exposed simultaneously to human lysozyme and IL-1 beta. Only pretreatment with human lysozyme abolished the lowering of the labelling index of the islet cell induced by IL-1 beta or by IL-1 beta and INF-gamma. Pycnotic nuclei were abundant in islets treated with IL-1 alone while they were not when islets were pretreated with human lysozyme. Chicken lysozyme had no protective effect in the same protocol. Human lysozyme was not protective when applied simultaneously with IL-1. Pretreatment of the islets by human lysozyme does not prevent the reduction of the insulin secretion induced by IL-1 beta. Human and chicken lysozyme differ further in their action when tested on fibroblasts proliferation. Only human lysozyme stimulates the latter. In conclusion, only human lysozyme seems to have a protective effect against the cytotoxicity of IL-1 in combination or not with IFN-gamma on islet cells in vitro. Moreover, to be protected, the islets have to be pretreated with lysozyme before the IL-1 application. Our in vitro results imply that natural aspecific immunity and its relation to the secretory function of the macrophage might be crucial for the prevention of the initial assault responsible for the onset of the immune process leading to insulin dependent diabetes.

Animals↗
PubMed1992

[Importance of diets and their effect on fetal development: function and structure of the endocrine pancreas following protein deficiency during intrauterine life].

When an isocaloric low protein diet (8% versus 20%) is administrated to rats during gestation, the fetus or the neonate has a lower body weight and the structure and function of the endocrine pancreas is altered: islet cell proliferation, islet size and islet vascularisation are reduced when compared with a control group. If these fetal islets are cultured during 7 days in vitro, they secrete less insulin than normal islets in response to an AA challenge. When these newborns are fed with a low protein diet until adult age and analyzed at 70 days, the same alterations of the endocrine pancreas persist: the in vitro insulin secretion of the isolated islets in response to AA is dramatically depressed although their response to glucose is normal. However in vivo glucose and insulin levels in response to oral glucose challenge are abnormal. In addition, permanent functional alterations seem to persist when induced in utero. A normal diet (20% protein) given from birth to adulthood does not restore a normal insulin response in vivo to an oral glucose challenge.

Animals↗
PubMed1991

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.

Aging↗