Type 2 diabetes (T2D) is one of the main current threats to human health. Both T2D and its numerous clinical complications are related to mitochondrial dysfunction and oxidative stress. Over the past decade, great progress has been made in extending our knowledge about the signaling events regulated by mitochondria. However, the links among mitochondrial impairment, oxidative stress, autophagy, endoplasmic

Endocrine disrupting chemicals (EDCs) are chemicals that can interfere with normal endocrine signals. Human exposure to EDCs is particularly concerning during vulnerable periods of life, such as pregnancy. However, often overlooked is the effect that EDCs may pose to the placenta. The abundance of hormone receptors makes the placenta highly sensitive to EDCs. We have reviewed the most recent advances

Genetic and molecular disparities between men and women have a role in the differing incidence, pathophysiology, clinical signs, and treatment outcome of several cancers. Sex differences in cancer incidence are attributed to regulation at the genetic/molecular level and to sex hormones that in turn modulate gene expression in various cancers. Sex differences in the incidence of cancer, its aggressiveness

Leptin-based obesity pharmacotherapies were originally developed according to the lipostatic view that elevated circulating leptin levels promote a negative energy balance. A series of independent preclinical findings suggest, however, that a partial reduction in circulating leptin levels (either by immunoneutralization, a peripherally restricted CB1 receptor inverse agonist, or bariatric surgery)

The prevalence of obesity and associated diseases has reached pandemic levels. Obesity is often associated with overnutrition and a sedentary lifestyle, but clearly other factors also increase the susceptibility of metabolic disease states. Ancestral and direct exposures to environmental toxicants and altered nutrition have been shown to increase susceptibility for obesity and metabolic dysregulation

Research over the past few decades has shed light on the mechanisms underlying the link between circadian disruption and the development of metabolic diseases such as obesity, type 2 diabetes, and cancer. However, how the clock network interacts with tissue-specific nutrient-sensing pathways during conditions of nutrient stress or pathological states remains incompletely understood. Recent work has

The tight coordination between mitochondrial biogenesis and mitophagy can be dysregulated during aging, critically influencing whole-body metabolism, health, and lifespan. To date, caloric restriction (CR) appears to be the most effective intervention strategy to improve mitochondrial turnover in aging organisms. The development of pharmacological mimetics of CR has gained attention as an attractive

Familial hypercholesterolemia (FH), mainly arising from loss-of-function mutation of the low-density lipoprotein receptor (LDLR), is a life-threatening inherited cardiometabolic disorder with limited therapies. In a recent study, Zhao et al. created a new model of FH and demonstrate that LDLR gene editing protects against both FH and atherosclerosis.

Glucagon-like peptide-1 (GLP-1) receptor agonists improve glucose homeostasis, reduce body weight, and over time benefit cardiovascular health in type 2 diabetes mellitus (T2DM). However, dose-related gastrointestinal effects limit efficacy, and therefore agents possessing GLP-1 pharmacology that can also target alternative pathways may expand the therapeutic index. One approach is to engineer GLP-1

Dietary patterns, microbiome dysbiosis, and gut microbial metabolites (GMMs) have a pivotal role in the homeostasis of intestinal epithelial cells and in disease progression, such as that of colorectal cancer (CRC). Although GMMs and microorganisms have crucial roles in many biological activities, models for deciphering diet–microbiome–host relationships are largely limited to animal models. Thus,

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is

Traditional methods for diabetes management require constant and tedious glucose monitoring (GM) and insulin injections, impacting quality of life. The global diabetic population is expected to increase to 439 million, with approximately US$490 billion in healthcare expenditures by 2030, imposing a significant burden on healthcare systems worldwide. Recent advances in nanotechnology have emerged as

Clonal hematopoiesis of indeterminate potential (CHIP), defined as a clone of hematopoietic cells consisting of a single acquired mutation during a lifetime, has recently been discovered to be a major risk factor for atherosclerotic cardiovascular disease (CVD). As such, this phenomenon has sparked interest into the role that these single mutations may play in CVD. Atherosclerotic CVD is a complex

Type 1 diabetes (T1D) patients show lipid disorders which are likely to play a role in their increased cardiovascular (CV) disease risk. Quantitative abnormalities of lipoproteins are noted in T1D with poor glycemic control. In T1D with optimal glycemic control, triglycerides and LDL-cholesterol are normal or slightly decreased whereas HDL-cholesterol is normal or slightly increased. T1D patients,

Müller cells are glia that play important regulatory roles in retinal metabolism. These roles have been evolutionarily conserved across at least 300 million years. Müller cells have a tightly locked metabolic signature in the healthy retina, which rapidly degrades in response to insult and disease. This variation in metabolic signature occurs in a chaotic fashion, involving some central metabolic pathways

The failure of insulin to suppress glucose production by the liver is a key aspect of the insulin resistance seen in type 2 diabetes. Lipid-activated protein kinase C epsilon has long been identified as an important mediator of diet-induced glucose intolerance and hepatic insulin resistance and the current view emphasizes a mechanism involving phosphorylation of the insulin receptor by the kinase to

Metformin has antidiabetic, anticancer, and prolongevity effects, but seems to interfere with aerobic training mitochondrial adaptations. The primary mechanism of action has been suggested to be the inhibition of mitochondrial complex I. Recent papers (Wang et al. and Cameron et al.), however, provide evidence to deny the hypothesis of a direct action of metformin on complex I.

Here I review vertebral fractures (VFs) as an emerging complication of acromegaly through a pathway of key questions in order to help clinicians manage the disease. Peculiarities of acromegalic osteopathy are that VFs are common but not explained by low bone mineral density (BMD) being related to disease duration and activity, and occurring even after remission.

In this opinion article we critically assess evidence for the existence of a family of antiangiogenic vascular endothelial growth factor (Vegfaxxxb) transcripts, arising from the use of a phylogenetically conserved alternative distal splice site within exon 8 of the VEGFA gene. We explain that prior evidence for Vegfaxxxb transcripts in tissues rests heavily upon flawed RT-PCR methodologies, with the

Diabetes and cardiovascular disease (CVD) have evolved as the leading cause of mortality and morbidity worldwide. In addition to traditional risk factors, recent studies have established that the human microbiota, particularly gut bacteria, plays a role in the development of diabetes and CVD. Although the presence of microbes in blood has been known for centuries, mounting evidence in this metagenomic

Obesity, a chronic inflammatory disease, is the most prevalent modifiable risk factor for cardiovascular disease. The mechanisms underlying inflammation in obesity are incompletely understood. Recent developments have challenged the dogma of immunological memory occurring exclusively in the adaptive immune system and show that the innate immune system has potential to be reprogrammed. This innate immune

The pituitary hormone prolactin (PRL) regulates a variety of functions beyond reproduction. The association between physiological (pregnancy) and pathological (prolactinoma) hyperprolactinemia and metabolic alterations led to the concept of this hormone being diabetogenic. However, large cohort clinical studies have recently shown that low circulating PRL levels are associated with metabolic disease

Glucocorticoids are steroid hormones that are of pivotal importance in human physiology. Glucocorticoid signaling is complex in nature and dependent on many interacting factors. As glucocorticoids exhibit sexually dimorphic effects on several key processes including in metabolism, crosstalk with the sex steroid hormones (androgens and estrogens) is relevant. In this review, we highlight the state-of-the-art

Meditation is a popular practice for reducing stress and improving mental health and wellbeing. Its effects are mediated largely by the endocrine system, including the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-thyroid axis, and the renin-angiotensin-aldosterone system, and energy homeostasis. The limited evidence available indicates that changes associated with endocrine function

The heart pumps blood throughout the whole life of an organism, without rest periods during which to replenish energy or detoxify. Hence, cardiomyocytes, the working units of the heart, have mechanisms to ensure constitutive production of energy and detoxification to preserve fitness and function for decades. Even more challenging, the heart must adapt to the varying conditions of the organism from

Genome-wide association studies (GWASs) have identified SNPs of the fat mass and obesity (FTO) gene as the most important risk alleles for obesity. However, how the presence of risk alleles affect phenotype is still a matter of intense investigation. In 2014, a study revealed that long-range enhancers from the intronic regions of the FTO gene regulate iroquois-class homeobox protein (IRX)3 expression

Controlled ovarian hyperstimulation (COH) determines an anticipation of endometrial maturation and a premature occurrence of the implantation window, as shown by histological, histochemical, and molecular studies and indirectly by clinical trials. There is growing agreement that in patients hyper-responding to COH and in those undergoing transfer at the blastocyst stage, deferring the transfer in a

Diabetes mellitus (DM) is a devastating metabolic disease. Stem cell therapy provides great hope to all diabetic patients. Umbilical cord (UC) Wharton's jelly mesenchymal stem cells (WJ-MSCs) specifically provides a potential cell therapy for DM. In this article, we discuss major advantages of WJ-MSCs and challenges facing their clinical utility in DM.

Raising HDL using cholesteryl ester transfer protein (CETP) inhibitors failed to show a clinically relevant risk reduction of cardiovascular disease in clinical trials, inviting reconsideration of the role of CETP and HDL in human physiology. Based on solid evidence from studies with isolated macrophages, rodents, and humans, we propose that a major function of CETP may be to modulate HDL in order

Chronic-diabetes-related complications simultaneously compromise both the micro- and macrovascular trees, with target organs considered as the paradigm of large vessel injury also entailing microangiopathic changes. However, complications independent or partially independent from vascular damage are often overlooked. This includes neuronal dysfunction (e.g., retinal neurodegeneration), interstitial

The past decade has witnessed a revival of interest in the hormone melatonin, partly attributable to the discovery that genetic variation in MTNR1B - the melatonin receptor gene - is a risk factor for impaired fasting glucose and type 2 diabetes (T2D). Despite intensive investigation, there is considerable confusion and seemingly conflicting data on the metabolic effects of melatonin and MTNR1B variation

The uterine luminal epithelium (LE) is the first maternal contact for an implanting embryo. Intrauterine fluid resorption, cessation of LE proliferation and apoptosis, and LE structural changes are prerequisites for establishing transient uterine receptivity for embryo implantation. Vesicle trafficking in the LE and receptor-mediated paracrine and autocrine mechanisms are crucial both for LE preparation

Eukaryotes must balance the metabolic and cell death actions of mitochondria via control of gene expression and cell fate by chromatin, thereby functionally binding the metabolome and epigenome. This interaction has far-reaching implications for chronic diseases in humans, the most common of which are those of the cardiovascular system. The most devastating consequence of cardiovascular disease, heart

Chile has experienced rapid epidemiological transitions characterized by decreasing infant mortality, population aging, and a shift towards obesity with an increase in noncommunicable diseases (NCDs). Today, tobacco, alcohol, and ultraprocessed foods are the main risk factors for these diseases. Based on Chile's experience in tobacco control, we discuss paths to make progress in population evidence-based

Over the past decade, several studies have shown that activity of extra-renal mineralocorticoid receptors (MR) regulates vascular tone, adipogenesis, adipose tissue function, and cardiomyocyte contraction. In mice, abnormal activation of MR in the vasculature and in adipose tissue favors the occurrence of several components of the metabolic syndrome (MetS), such as hypertension, obesity, and glucose

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are increasingly recognized, characterized by prolonged survival even with metastatic disease. Their medical treatment is complex involving various specialties, necessitating awareness of treatment-related adverse effects (AEs). As GEP-NENs express somatostatin receptors (SSTRs), long-acting somatostatin analogs (SSAs) that are used for secretory

The tumor microenvironment (TME) is an attractive target to develop novel strategies for hormone-dependent cancers. Several molecules in the TME can favor tumor development and progression, including lipoproteins. Lipoproteins are taken up by cancer cells, providing them with cholesterol and fatty acids. Cholesterol regulates cell signaling and it is converted into a series of bioactive metabolites

Individuals with type 1 diabetes (T1D) frequently fail to achieve glycemic goals and have excess cardiovascular risk and premature death. Adjunctive agents may play a role in reducing morbidity, mortality, and the adverse sequelae of insulin treatment. A surge in type 2 diabetes drug development has revealed agents with benefits beyond glucose lowering, including cardiovascular risk reduction. Could

Epidemiological studies have revealed that caffeine consumption during pregnancy is associated with adverse gestational outcomes, yet the underlying mechanisms remain obscure. Recent animal studies with physiologically relevant dosages have begun to dissect adverse effects of caffeine during pregnancy with respect to oviduct contractility, embryo development, uterine receptivity, and placentation that

Chest pain with non-obstructive coronary artery disease (NOCAD) occurs more frequently in women than in men and is mainly related to coronary microvascular disease (CMD). The majority of CMD patients are postmenopausal women, suggesting a role for lack of estrogens in the development and progression of CMD. Patients are often discharged without a clear treatment plan due to the limited understanding

In their recent study, Nicholas et al. challenge the current dogma that T cell inflammation must be fueled by glycolysis and demonstrate a novel metabolic mechanism for Th17 inflammation in human type 2 diabetes mellitus (T2DM): a combination of increased environmental long-chain fatty acid metabolites coupled with decreased fatty acid oxidation.

Methylglyoxal (MG) is a ubiquitous metabolite that spontaneously reacts with biopolymers forming advanced glycation end-products (AGEs). AGEs are strongly associated with aging-related diseases, including cancer, neurodegenerative diseases, and diabetes. As the formation of AGEs is nonenzymatic, the damage caused by MG and AGEs has been regarded as unspecific. This may have resulted in the field generally

Globally, obesity has reached epidemic proportions. The rapidly increasing numbers of overweight people can be traced back to overconsumption of energy-dense, poor-quality foods as well as physical inactivity. This development has far-reaching and costly implications. Not only is obesity associated with serious physiological and psychological complications, but mounting evidence also indicates a ripple

Members of the nuclear receptor superfamily serve as master regulators in signaling by either positively or negatively regulating gene expression. Accumulating evidence has suggested that nuclear receptors are actively involved in immune responses, with specific roles in different immune cell compartments that contribute to both normal function and to disease development. The druggable properties of

Activity of the hypothalamic–pituitary–adrenal (HPA) axis is tuned by corticosteroid feedback. Corticosteroids regulate cellular function via genomic and nongenomic mechanisms, which operate over diverse time scales. This review summarizes recent advances in our understanding of how corticosteroid feedback regulates hypothalamic stress neuron function and output through synaptic plasticity, changes

The glucocorticoid receptor (GR) has been shown to be important for mediating cellular responses to stress and circulating glucocorticoids. Ligand-dependent transcriptional changes induced by GR are observed across numerous tissues. However, the mechanisms by which GR achieves cell and tissue-specific effects are less clear. Epigenetic mechanisms have been proposed to explain some of these differences

Discovery of the satiety hormone leptin in 1994 and its characterization in mammals provided a key tool to deciphering the complex mechanism governing adipose tissue regulation of appetite and energy expenditure. Surprisingly, despite the perfectly logical notion of an energy-storing tissue announcing the amount of fat stores using leptin signaling, alternate mechanisms were chosen in bird evolution

Kisspeptin (KP) plays a major role in the regulation of reproduction governed by the hypothalamic–pituitary–gonadal (HPG) axis. However, recent findings suggest that the KP system is present not only centrally (at the level of the hypothalamus), but also in the peripheral organs crucial for the control of metabolism. The KP system is sexually differentiated in the hypothalamus, and it is of particular

The parathyroid hormone (PTH) type 1 receptor (PTHR) is the canonical G protein-coupled receptor (GPCR) for PTH and PTH-related protein (PTHrP) and the key regulator of calcium homeostasis and bone turnover. PTHR function is critical for human health to maintain homeostatic control of ionized serum Ca2+ levels and has several unusual signaling features, such as endosomal cAMP signaling, that are well-studied

Autophagy contributes to cellular quality control and energetics through lysosomal breakdown and recycling of essential cellular components. Chaperone-mediated autophagy (CMA) adds to these autophagic functions the ability to timely and selectively degrade single tagged proteins to terminate their cellular function and, in this way, participate in the regulation of multiple cellular processes. Many

The target of rapamycin complex 2 (TORC2) was discovered in 2002 in budding yeast. Its mammalian counterpart, mTORC2, was first described in 2004. Soon thereafter it was demonstrated that mTORC2 directly phosphorylates Akt on Ser473, ending a long search for the elusive 'second' insulin-responsive Akt kinase. In this review we discuss key evidence pertaining to the subcellular localization of mTORC2

Nitric oxide (NO) contributes to carbohydrate metabolism and decreased NO bioavailability is involved in the development of type 2 diabetes mellitus (T2DM). NO donors may improve insulin signaling and glucose homeostasis in T2DM and insulin resistance (IR), suggesting the potential clinical importance of NO-based interventions. In this review, site-specific roles of the NO synthase (NOS)-NO pathway

The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiology and metabolism. However, the mechanisms that underlie these observations remain largely unknown. Recent findings

Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion

Aging is a global decline of physiological functions, leading to an increased susceptibility to diseases and ultimately death. Maximum lifespans differ up to 200-fold between mammalian species. Although considerable progress has been achieved in identifying conserved pathways that regulate individual lifespan within model organisms, whether the same pathways are responsible for the interspecies differences

The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for

The growth hormone (GH) and insulin-like growth factor-1 (IGF1) axis is the key regulator of longitudinal growth, promoting postnatal bone and muscle growth. The available data suggest that GH expression by tumour cells is associated with the aetiology and progression of various cancers such as endometrial, breast, liver, prostate, and colon cancer. Accordingly there has been increased interest in

Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence

Diabetes is rapidly emerging as one of the biggest health concerns worldwide, with profound implications for disability, mortality, and costs. This suddenly escalating rate of diabetes correlates with global industrialization and the production of plastics, pesticides, synthetic fertilizers, electronic waste, and food additives that release endocrine-disrupting chemicals (EDCs) into the environment