Review Programming of the endocrine pancreas by the early nutritional environment (original) (raw)
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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.
Endocrinology, 2016
Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P Ͻ .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P Ͻ .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P Ͻ .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P Ͻ .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.
Intrauterine programming of the endocrine pancreas
Diabetes, Obesity and Metabolism, 2007
Epidemiological studies have revealed strong relationships between poor foetal growth and subsequent development of the metabolic syndrome. Persisting effects of early malnutrition become translated into pathology, thereby determine chronic risk for developing glucose intolerance and diabetes. These epidemiological observations identify the phenomena of foetal programming without explaining the underlying mechanisms that establish the causal link. Animal models have been established and studies have demonstrated that reduction in the availability of nutrients during foetal development programs the endocrine pancreas and insulin-sensitive tissues. Whatever the type of foetal malnutrition, whether there are not enough calories or protein in food or after placental deficiency, malnourished pups are born with a defect in their b-cell population that will never completely recover, and insulin-sensitive tissues will be definitively altered. Despite the similar endpoint, different cellular and physiological mechanisms are proposed. Hormones operative during foetal life like insulin itself, insulin-like growth factors and glucocorticoids, as well as specific molecules like taurine, or islet vascularization were implicated as possible factors amplifying the defect. The molecular mechanisms responsible for intrauterine programming of the b cells are still elusive, but two hypotheses recently emerged: the first one implies programming of mitochondria and the second, epigenetic regulation.
Fetal programming of glucose–insulin metabolism
Molecular and Cellular Endocrinology, 2009
Epidemiological studies have shown a link between poor fetal growth and increased risk of developing type 2 diabetes. These observations are highly reproducible in many populations worldwide although the mechanisms behind them remain elusive.
Biochemical Journal, 2000
There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids) markedly influence intra-uterine growth and development. A picture is also emerging of the biochemical and physiological mechanisms that may underlie these effects. This review focuses on recent research directed towards understanding the molecular basis of the relationship between indices of poor early growth and the subsequent development of glucose intolerance and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal environment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-β-cell insulin secretion and the sensitivity to insulin of...
The Journal of Physiology, 2004
The incidence of the metabolic syndrome, a cluster of abnormalities focusing on insulin resistance and associated with high risk for cardiovascular disease and diabetes, is reaching epidemic proportions. Prevalent in both developed and developing countries, the metabolic syndrome has largely been attributed to altered dietary and lifestyle factors that favour the development of central obesity. However, population-based studies have suggested that predisposition to the metabolic syndrome may be acquired very early in development through inappropriate fetal or neonatal nutrition. Further evidence for developmental programming of the metabolic syndrome has now been suggested by animal studies in which the fetal environment has been manipulated through altered maternal dietary intake or modification of uterine artery blood flow. This review examines these studies and assesses whether the metabolic syndrome can be reliably induced by the interventions made. The validity of the different species, diets, feeding regimes and end-point measures used is also discussed.
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.
Endocrine and metabolic programming during intrauterine development
Early Human Development, 2005
In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. Many of these metabolic disorders have an endocrine origin and are accompanied by abnormal hormone concentrations. This has led to the hypothesis that adult metabolic disease arises in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions associated with fetal growth retardation. This review examines the experimental evidence for prenatal endocrine programming with particular emphasis on endocrine axes involved in growth and metabolism, namely, the hypothalamic-pituitaryadrenal axis, the endocrine pancreas and the somatotrophic axis. It also considers how changes in these endocrine systems contribute to the programming of metabolism in later life. D
2016
Aims/hypothesis: The incidence of type 2 diabetes (T2D) is increasing globally. T2D is characterised by progressive deterioration of glycaemic control. These changes in glucose homeostasis are primarily due to β-cell secretory dysfunction and/or peripheral insulin resistance. Studies show that maternal health directly influences foetal development and birth outcomes. Malnutrition of the growing foetus may lead to development of T2D and other metabolic diseases later in life. Consequently, several studies have reported that maternal diet programmes the foetus leading to altered physiology and metabolism in the offspring. Foetal programming refers to the exposure to a stimulus and/or insult during the critical periods of development i.e. foetal and early neonatal life. We therefore sought to ascertain how a dietary fat content in maternal diet affects foetal programming and its contribution to the pathogenesis of T2D of the offspring. Methods: Pregnant rats were randomly grouped and maintained on diets varying in fat content: 10% (Control), 20% (20F), 30% (30F) and 40% (40F) fat throughout their pregnancy. Pancreata were collected and quantitative polymerase chain reaction tests were performed to determine the mRNA expression profiles of the insulin signaling and transcription factors including Pdx1, MafB, IRα, insulin and glucagon. Other pancreata were immunostained followed by image analysis of these factors. Results: In 40F neonates, Ins1, Ins2, glucagon, MafB and IRS2 mRNA expression was reduced. Further, in 30F neonates, Ins1, Pdx1 and MafB mRNA expression was reduced. There were no changes in immunoreactivity for the factors studied. However, when separating the offspring according to gender, IRα immunoreactivity was reduced in 40F females compared to 40F males. Conclusion: Continuous exposure of pregnant rats to an excessively high fat diet impairs gene expression of key factors involved in insulin signaling and islet development in their neonatal offspring. This reflects foetal programming of metabolic pathways in insulin signaling and β-cell development and function which potentially renders these offspring susceptible to metabolic disease and the development of T2D.
American journal of physiology. Endocrinology and metabolism, 2014
Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, ...