Nutritional influences on pancreatic development and potential links with non-insulin-dependent diabetes (original) (raw)
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Review Programming of the endocrine pancreas by the early nutritional environment
2005
A substantial body of evidence now suggests that poor intrauterine milieu elicited by maternal nutritional disturbance or placental insufficiency may programme susceptibility in the foetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. Further data showing the developmental programming of the metabolic syndrome are now available thanks to animal studies in which the foetal environment has been manipulated. This review examines the developmental programming of glucose intolerance by disturbed intrauterine metabolic condition in rats. It focuses on the alteration of the endocrine pancreas at birth. Long-term consequences, deterioration of glucose tolerance and even transgenerational effects are reported. Maternal protein, caloric restriction and diabetes during gestation/lactation lead to altered �-cell mass. This review also tempts to identify cellular and molecular mechanisms involved in this process.
Programming of the endocrine pancreas by the early nutritional environment
The International Journal of Biochemistry & Cell Biology, 2006
A substantial body of evidence now suggests that poor intrauterine milieu elicited by maternal nutritional disturbance or placental insufficiency may programme susceptibility in the foetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. Further data showing the developmental programming of the metabolic syndrome are now available thanks to animal studies in which the foetal environment has been manipulated. This review examines the developmental programming of glucose intolerance by disturbed intrauterine metabolic condition in rats. It focuses on the alteration of the endocrine pancreas at birth. Long-term consequences, deterioration of glucose tolerance and even transgenerational effects are reported. Maternal protein, caloric restriction and diabetes during gestation/lactation lead to altered -cell mass. This review also tempts to identify cellular and molecular mechanisms involved in this process.
Endocrine pancreatic development: impact of obesity and diet
Frontiers in physiology, 2013
During embryonic development, multipotent endodermal cells differentiate to form the pancreas. Islet cell clusters arising from the pancreatic bud form the acini tissue and exocrine ducts whilst pancreatic islets form around the edges of the clusters. The successive steps of islet differentiation are controlled by a complex network of transcription factors and signals that influence cell differentiation, growth and lineage. A Westernized lifestyle has led to an increased consumption of a high saturated fat diet, and an increase in maternal obesity. The developing fetus is highly sensitive to the intrauterine environment, therefore any alteration in maternal nutrition during gestation and lactation which affects the in-utero environment during the key developmental phases of the pancreas may change the factors controlling β-cell development and β-cell mass. Whilst the molecular mechanisms behind the adaptive programming of β-cells are still poorly understood it is established that ch...
Maternal malnutrition programs the endocrine pancreas in progeny
The American Journal of Clinical Nutrition, 2011
Type 2 diabetes arises when the endocrine pancreas fails to secrete sufficient insulin to cope with metabolic demands resulting from b cell secretory dysfunction, decreased b cell mass, or both. Epidemiologic studies have shown strong relations between poor fetal and early postnatal nutrition and susceptibility to diabetes later in life. Animal models have been established, and studies have shown that a reduction in the availability of nutrients during fetal development programs the endocrine pancreas and insulin-sensitive tissues. We investigated several modes of early malnutrition in rats. Regardless of the type of diet investigated, whether there was a deficit in calories or protein in food or even in the presence of a high-fat diet, malnourished pups were born with a defect in their b cell population, with fewer b cells that did not secrete enough insulin and that were more vulnerable to oxidative stress; such populations of b cells will never completely recover. Despite the similar endpoint, the cellular and physiologic mechanisms that contribute to alterations in b cell mass differ depending on the nature of the nutritional insult. Hormones that are operative during fetal life, such as insulin, insulin-like growth factors, and glucocorticoids; specific molecules, such as taurine; and islet vascularization have been implicated as possible factors in amplifying this defect. The molecular mechanisms responsible for intrauterine programming of b cells are still elusive, but among them the programming of mitochondria may be a strong central candidate. Am J Clin Nutr 2011;94(suppl):1824S-9S.
Journal of Endocrinology, 2006
Restriction of dietary protein during gestation and lactation in the rat results in a reduction in b cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP ). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 mm 2 ) and medium (between 5000 and 10 000 mm 2 ) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of b cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in midgestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both b cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP , but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of b cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of b cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.
Foetal development of the pancreas
PubMed, 2010
In the present study, we aimed to gather morphometric data on the localisation and development of the pancreas during the foetal period. The study was carried out on 222 human foetuses aged 9-40 weeks of gestation with no external pathology or anomaly. The abdominal wall was dissected after general external measurements of the foetuses were carried out. Data on the localisation of the pancreas in the abdominal cavity and its localisation relative to the median plane, xiphoid process, and umbilicus were acquired and various morphometric parameters including the length of the pancreas and heights of the head and body of the pancreas were measured. It was found that, in the foetal period, the foetal pancreas was primarily accumulated on the transverse plane passing through the umbilicus, and on the other quadrants. Means and standard deviations of all morphometric parameters were calculated for each gestational week, month, and trimester. There were significant relations between the parameters and gestational age (p < 0.001). There were no differences in any of the parameters between sexes (p > 0.05). In conclusion, morphometric and location data on foetal pancreases acquired in the present study will contribute to other studies carried out in obstetrics, perinatology, forensic medicine, and foetal pathology departments, aimed at identifying anomalies, pathologies, and variations of the pancreas and treatment of such cases.
Clinical Science, 2004
Poor fetal and infant nutrition has been linked to impaired glucose tolerance in later life. We studied the effect of protein deficiency during gestation and the suckling period in a rat model and found that poor nutrition ‘programmes’ pancreatic β-cell GK (glucokinase; known as the glucose sensor) and glucose-stimulated insulin secretion response in newborn, suckling and adult rat offspring. Pregnant female rats were divided into three groups: a control group was kept on a normal protein (20%) diet, another group was fed a low-protein (LP) (6%) diet during gestation and suckling periods (LP-G + S group) and another was fed a LP diet during gestation then a normal protein diet during the suckling period (LP-G group). The pulsatile glucose-stimulated insulin secretion response was acutely disrupted and the peak insulin secretion was markedly decreased in newborn and 3-week-old offspring of the LP-G + S group compared with the control group. Also, there was an altered pulsatile secret...
Ontogeny of pancreatic exocrine function
Archives of Disease in Childhood, 1990
Exocrine pancreatic proteolytic activity, determined by serial measurement of faecal chymotrypsin concentration, was investigated in 21 preterm infants (23-32 weeks' gestation) during the first 28 days of life. The overall chymotrypsin concentration range was similar to that already described in term infants showing that pancreatic chymotrypsin secretion is equally well developed at birth in the preterm infant. A chymotrypsin concentration peak, seen in term infants at 4 days, did not occur in this study until day 8, suggesting a slower initiation of pancreatic exocrine function in the preterm infant. Median faecal chymotrypsin concentrations, calculated for each baby using data from stools passed between day 2 and day 12 of life, were significantly lower in infants who were small for gestational age when compared with those who were an appropriate size for gestational age. The lower chymotrypsin concentration in infants who were small for gestational age suggests a deleterious effect of intrauterine growth retardation on pancreatic exocrine function which may be a factor in limiting postnatal catch up growth.
The ontogeny of the endocrine pancreas in the fetal/newborn baboon
The Journal of endocrinology, 2012
Erratic regulation of glucose metabolism including hyperglycemia is a common condition in premature infants and is associated with increased morbidity and mortality. The objective of this study was to examine histological and ultrastructural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons. Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140d GA, or 175d GA. Eight animals were delivered at term (185d GA); half were fed for 5 days. Seventy-three nondiabetic adult baboons were used for comparison. Pancreatic tissue was studied using light microscopy, confocal imaging, and electron microscopy. The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of a-b-d-cell type were similar within each fetal and newborn GA (NS) but were higher than the adults (P!0 . 05) regardless of GA. The ratio of b cells within the islet (whole and core) increased with gestation (P!0 . 01). Neonatal baboons, which survived for 5 days (feeding), had a 2 . 5-fold increase in pancreas weight compared with their counterparts killed at birth (PZ0 . 01). Endocrine cells were also found in exocrine ductal and acinar cells in 125, 140 and 175d GA fetuses. Subpopulation of tissue that coexpressed trypsin and glucagon/insulin shows the presence of cells with mixed endo-exocrine lineage in fetuses. In summary, the fetal endocrine pancreas has no prevalence of a a-b-d-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long-term implications.