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Диабет Mellitus и энергетический дисметаболизм в болезни Альцгеймера: понимание отношений и потенциальных терапевтических целей.

За последнее столетие в мире наблюдалось постепенное, но устойчивое увеличение средней продолжительности жизни. Следствием увеличения продолжительности жизни является связанный с этим рост распространенности связанных с возрастом хронических изнурительных нейродегенеративных расстройств, таких, как болезнь Альцгеймера (АБ), болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Эти расстройства, которые, как правило, характеризуются потерей моторных/сенсорных нейронов и когнитивной отсталостью, по-прежнему смущают исследователей, которые неустанно работают над определением своих пато

Совпадение в аннотации оригинала
Over the last century, there has been a gradual but sustained increase in life expectancy globally. A consequence of increased life expectan … metabolism have been linked to the aetiopathogenesis of AD. Moreover, metabolic hormones, including ghrelin, leptin, insulin, and insulin-like growth factor (IGF)-1, have been reported to play key roles in the regulation of neuronal injury and loss in neurodegenerative diseases like AD. In this narrative review, we examine the current scientific evidence …

Pharmacotherapeutic advances for chronic idiopathic constipation in adults.

INTRODUCTION: Chronic idiopathic constipation is a common gastrointestinal disorder whose treatment is still far from being satisfactory for … 5-HT4 agonists velusetrag and naronapride are in advanced development. In addition, relamorelin, a ghrelin agonist, seems promising for accelerating colonic transit. EXPERT OPINION: Several new promising drugs have been released with the potential to be effective in the treatment of chronic idiopathic constipation. On the other hand, the experience with …

The role of insufficient sleep and circadian misalignment in obesity.

Traditional risk factors for obesity and the metabolic syndrome, such as excess energy intake and lack of physical activity, cannot fully ex … impact of insufficient sleep and circadian misalignment in humans on appetite hormones (focusing on ghrelin, leptin and peptide-YY), energy expenditure, food intake and choice, and risk of obesity. Some potential strategies to reduce the adverse effects of sleep disruption on metabolic health are provided and future research priorities are highlighted. Mi …

Precision Medicine Approaches to Prevent Gastric Cancer.

Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The p … levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutti …

Stimulation of Gastric Transit Function Driven by Hydrolyzed Casein Increases Small Intestinal Carbohydrate Availability and Its Microbial Metabolism.

Gastrointestinal (GI) functions affect gut nutrient flow and microbial metabolism. Dietary peptides modulate GI functions and improve small … ity in ileal digesta. To unveil the mechanisms, it is found that the hydrolyzed casein enhances the ghrelin signal and improves development of interstitial cells of Cajal and muscular layer in gastric corpus, indicating the enhanced upper GI transit function. In addition, hydrolyzed casein improves small intestinal health, as indicated by higher villus he …

Insulin Resistance Is Associated with Reduced Food Odor Sensitivity across a Wide Range of Body Weights.

The worldwide obesity epidemic is a major health problem driven by the modern food environment. Recently, it has been shown that smell perce … response to food intake, we assessed pre- and postprandial levels of insulin, leptin, glucose, and ghrelin. Odor sensitivity did not directly depend on body weight status/body mass index (BMI) or hunger state. However, we could establish a strong negative mediating effect of insulin resistance on the relationship between BMI/waist-hip ratio and olfactory …

The regulatory approval of anamorelin for treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer in Japan: facts and numbers.

Anamorelin is a ghrelin receptor agonist that can be administered orally and thought to improve cancer cachexia by improving appetite and increasing serum insulin-like growth factor-1. Anamorelin was not approved for use in Europe. In contrast, the use of anamorelin for cancer cachexia in four types of cancer (non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer) was approved in Japan on 11 December 2020. Phase 2 trial (ONO-7643-04) for the treatment of patients with non-small cell lung cancer and cachexia resulted in 1.56 kg lean body mass increase assessed by …

Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials.

Introduction: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been … relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their ph …

Endocrine and metabolic disorders in patients with Gaucher disease type 1: a review.

BACKGROUND: Gaucher disease (GD) is one of the most prevalent lysosomal storage diseases and is associated with hormonal and metabolic abnormalities, including nutritional status disorders, hypermetabolic state with high resting energy expenditures, peripheral insulin resistance, hypoadiponectinaemia, leptin and ghrelin impairments, hypolipidaemia, linear growth deceleration and growth hormone deficiency, delayed puberty, hypocalcaemia and vitamin D deficiency. Specific treatments for GD such as enzyme replacement therapy and substrate reduction therapy display significant effects on the metab…

Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

BACKGROUND: Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposit … formed. RESULTS: The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protei …

Cytokines and male infertility.

Many male infertility cases have no apparent cause, being characterized as idiopathic. Both inflammation and obesity have long been associat … al and peripheral levels. In this regard, resistin, visfatin and the GH secretagogue peptic hormone ghrelin affect spermatogenesis, whereas data on adiponectin are rather scarce. In conclusion, inflammatory cytokines and adipokines seem to have a pivotal role in the regulation of spermatogenesis; any imbalance in this stable environment may lead to infert …

Sarcopenia associated with chemotherapy and targeted agents for cancer therapy.

Clinicians often believe that cachexia is caused by cancer and anorexia as a toxicity of chemotherapy or targeted anti-cancer agents. It is … depleted, omega-3 fatty acids, testosterone and selective androgen receptor modulators (SARMS) and ghrelin. A comprehensive multimodal and multiple drug approach is likely to be better than single modalities. However, this is yet to be proven. Finally, it is not known if intervening to prevent or reverse sarcopenia will have a clinical benefit in terms o …

Anorexia Nervosa and Its Associated Endocrinopathy in Young People.

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include … r restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Phys …

Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice.

Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these p … eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the …

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years.

At the time of the publication of Geoffrey Harris's monograph on 'Neural control of the pituitary gland' 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood …

Cancer cachexia, mechanism and treatment.

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adi … cise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options in …

Effect of a test meal on meal responses of satiation hormones and their association to insulin resistance in obese adolescents.

OBJECTIVE: The role of gastrointestinal (GI) hormones in the pathophysiology of obesity is unclear, although they are involved in the regulation of satiation and glucose metabolism. To (i) examine glucagon-like peptide 1 (GLP-1), amylin, ghrelin, and glucagon responses to a meal in obese adolescents and to (ii) test which GI peptides are associated with insulin resistance are presented. METHODS: A total of 16 obese (body mass index (BMI) ≥ 97th percentile for age and gender) and 14 control (BMI between 25th and 75th percentiles) adolescents were included. Subjects were instructed to eat a tes…

Resistin -420C>G promoter variant and colorectal cancer risk.

PURPOSES: Obesity is associated with an increased risk of colorectal cancer (CRC), and ghrelin (GHRL) and resistin (RETN) are thought to be related to obesity. Our aim was to investigate whether GHRL and RETN gene variants are associated with CRC risk. MATERIALS AND METHODS: All 414 subjects, including 197 cases with CRC and 217 controls, were genotyped for the GHRL (rs26802) and RETN (rs1862513) or -420 C>G gene variants using the PCR-RFLP method. RESULTS: Our findings indicated that the RETN -420 C>G "CC" genotype, compared with the "GG" and "GC" genotypes, was a marker of decreased CRC su…

Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force.

BACKGROUND: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently pred … temic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-center …

Prevalence, incidence and clinical impact of cachexia: facts and numbers-update 2014.

Cachexia is a serious but underrecognised consequence of many chronic diseases. Its prevalence ranges from 5-15 % in end-stage chronic heart … proaches to treatment have failed to live up to the challenge of phase III clinical trials, but the ghrelin receptor agonist anamorelin seems to have fulfilled at least some early promise. Further advances are urgently needed.