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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.
Placenta 2002 Apr
PMID:Role of leptin in pregnancy--a review. 1197 63

Oxidative stress has been clearly linked to type 2 diabetes mellitus, however, limited data are available on the involvement of oxidative stress in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The aim of this study was to investigate the status of placental oxidative stress in healthy pregnant women and women with GDM. The hypothesis to be tested was that tissue markers of oxidative stress are significantly increased in GDM compared to normal placental tissues. Markers of oxidative stress measured were the release of 8-isoprostane (8-epi-prostaglandin F(2alpha)) from human term placental explants (n=11), the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase (n=10), and protein carbonyl content (n=12). Placental release of 8-isoprostane was 2-fold greater from women with GDM (P<0.001) compared to healthy pregnant women. Superoxide dismutase activity and protein carbonyl content were elevated in placentae obtained from women with GDM (P<0.04 and P<0.004 respectively), whilst there was no significant difference in the activity of glutathione peroxidase. These data demonstrate the presence of oxidative stress in the placenta from women with GDM, in addition to the induction of a key antioxidant, collectively indicating a state of existing oxidative stress in this condition.
Placenta 2004 Jan
PMID:Altered placental oxidative stress status in gestational diabetes mellitus. 1501 42

Research on intrauterine growth restriction (IUGR) and subsequent development of obesity, type 2 diabetes and the metabolic syndrome is rapidly expanding, and potential implications for primary prevention are considerable. We have critically appraised one of the experimental animal models frequently used as mimic of human fetal growth restriction, which involves bilateral ligation of the uterine artery in rats (Lig). Our experimental study showed that Lig performed on day 17 of pregnancy neither leads to IUGR nor to neonatal catch-up growth, an important pathogenetic co-factor in humans. Meta-analysis of the literature revealed domination by studies in which Lig pups with IUGR were actively selected. Accordingly, publication bias is evident (p=0.007). Altered placental perfusion--the main cause of IUGR in humans in Western countries--neither led to IUGR nor to neonatal catch-up growth in Lig offspring, i.e., to none of the etiological factors of the human 'small baby syndrome'. Appropriate and reproducible rodent models of IUGR through decreased placental flow remain to be established to uncover the pathophysiological basis of the 'small baby syndrome'. This may lead to new strategies of primary prevention of diabetes, obesity, and the metabolic syndrome.
Placenta 2008 Mar
PMID:Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: a critical appraisal of the experimental evidence. 1820 35

Being born small due to poor growth before birth increases the risk of developing metabolic disease, including type 2 diabetes, in later life. Inadequate insulin secretion and decreasing insulin sensitivity contribute to this increased diabetes risk. Impaired placental growth, development and function are major causes of impaired fetal growth and development and therefore of IUGR. Restricted placental growth (PR) and function in non-human animals induces similar changes in insulin secretion and sensitivity as in human IUGR, making these valuable tools to investigate the underlying mechanisms and to test interventions to prevent or ameliorate the risk of disease after IUGR. Epigenetic changes induced by an adverse fetal environment are strongly implicated as causes of later impaired insulin action. These have been well-characterised in the PR rat, where impaired insulin secretion is linked to epigenetic changes at the Pdx-1 promotor and reduced expression of this transcription factor. Present research is particularly focussed on developing intervention strategies to prevent or reverse epigenetic changes, and normalise gene expression and insulin action after PR, in order to translate this to treatments to improve outcomes in human IUGR.
Placenta 2010 Mar
PMID:Review: Placental programming of postnatal diabetes and impaired insulin action after IUGR. 2009 55

Maternal obesity is growing in prevalence and is associated with increased morbidity and mortality for both mother and child. Women who are obese during pregnancy have a greater risk of metabolic complications such as gestational diabetes mellitus (GDM) as well as type 2 diabetes after pregnancy. Children of obese and/or GDM mothers have an increased susceptibility to congenital abnormalities and a range of cardio-metabolic disorders. The placenta is at the interface of the maternal and fetal environments and, its function per se, plays a major role in dictating the impact of maternal health on fetal development. Here, we review the literature on how placental function is affected in pregnancies complicated by obesity, and pre-gestational and gestational diabetes. The focus is on the availability of three key substrates in these conditions: glucose, lipids, and amino acids, and their impact on placental metabolic activity. Maternal obesity and diabetes are not always associated with fetal compromise and the adaptation of the placenta may partially determine the outcome. Understanding the differences in metabolic adaptation may open avenues for therapeutic development.
Placenta 2017 06
PMID:Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes. 2799 98

Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology.
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PMID:Role of leptin as a link between metabolism and the immune system. 2828 98

Pregnancy is a remarkable physiological state, during which the metabolic system of the mother adapts to ensure that nutrients are made available for transfer to the fetus for growth and development. Adaptations of maternal metabolism during pregnancy are influenced by the metabolic and nutritional status of the mother and the production of endocrine factors by the placenta that exert metabolic effects. Insufficient or inappropriate adaptations in maternal metabolism during pregnancy may lead to pregnancy complications with important short- and long-term effects for both the health of the child and mother. This is very evident in gestational diabetes, which is marked by greater glucose intolerance and insulin resistance above that expected of a normal pregnancy. Gestational diabetes is associated with increased fetal weight and/or increased adiposity, higher instrumented delivery rates and greater risks for both mother and child of developing type 2 diabetes in the long-term. However, despite the negative health impacts of such metabolic imbalances during pregnancy, the precise mechanisms responsible for orchestrating these changes remain largely unknown. The present review describes the dynamic pregnancy-specific changes that occur in the metabolic system of the mother during pregnancy. It also discusses findings using surgical, pharmacological, genetic and dietary methods in experimental animals that highlight the role of pathways in maternal tissues that lead to metabolic dysfunction, with a particular focus on gestational diabetes. Finally, it summarises the work largely employing gene targeting and hormone administration in rodents that have illuminated the involvement of placental endocrine function in driving maternal metabolic adaptations. While current animal models may not fully replicate what is observed in humans, these have been instrumental in showing that there is a dynamic interplay between changes in maternal metabolic physiology and the placental production of endocrine factors that govern the availability of nutrients to the growing fetus. However, more work is required to specifically identify the placenta-driven changes in maternal metabolic physiology that ensure the appropriate level of insulin production and action during pregnancy. In doing so, these studies may pave the way to understanding the development of pregnancy complications like gestational diabetes, as well as further our understanding of type-2 diabetes and the control of metabolic physiology more broadly.
Placenta 2020 09 01
PMID:Exploring the causes and consequences of maternal metabolic maladaptations during pregnancy: Lessons from animal models. 3303 31