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Experimental and clinical endocrinology and diabetes
J.A. Barth
Experimental and clinical endocrinology and diabetes

J.A. Barth

0947-7349

Experimental and clinical endocrinology and diabetes/Journal Experimental and clinical endocrinology and diabetes
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    Experimental and Clinical Endocrinology & Diabetes Junior Editors

    Karsten MüssigCora WeigertMartin Reincke
    1页
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Young Awardees in Endocrinology Presenting Hot Topics

    Martin ReinckeHeike Biebermann
    2页
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

    Nicole BechmannGraeme Eisenhofer
    8页
    查看更多>>摘要：Germline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6–6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Obesity – A Matter of Motivation?

    Ruth HanssenSharmili E ThanarajahMarc TittgemeyerJens C. Brüning...
    6页
    查看更多>>摘要：Excessive food intake and reduced physical activity have long been established as primary causes of obesity. However, the underlying mechanisms causing this unhealthy behavior characterized by heightened motivation for food but not for physical effort are unclear. Despite the common unjustified stigmatization that obesity is a result of laziness and lack of discipline, it is becoming increasingly clear that high-fat diet feeding and obesity cause alterations in brain circuits that are critical for the control of motivational behavior. In this mini-review, we provide a comprehensive overview of incentive motivation, its neural encoding in the dopaminergic mesolimbic system as well as its metabolic modulation with a focus on derangements of incentive motivation in obesity. We further discuss the emerging field of metabolic interventions to counteract motivational deficits and their potential clinical implications.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    What is the Role of Thyroid Hormone Receptor Alpha 2 (TRα2) in Human Physiology?

    Sarah PaisdziorMarkus SchuelkeHeiko Krude
    7页
    查看更多>>摘要：Thyroid hormone receptors are nuclear receptors that function as transcription factors and are regulated by thyroid hormones. To date, a number of variants and isoforms are known. This review focuses on the thyroid hormone receptor α (TRα), in particular TRα2, an isoform that arises from alternative splicing of the THRA mRNA transcript. Unlike the TRα1 isoform, which can bind T3, the TRα2 isoform lacks a ligand-binding domain but still binds to DNA thereby antagonizing the transcriptional activity of TRα1. Although a regulatory role has been proposed, the physiological function of this TRα2 antagonism is still unclear due to limited in vitro and mouse model data. Recently, the first patients with resistance to thyroid hormone due to mutations in THRA, the TRα encoding gene, affecting the antagonistic function of TRα2 were described, suggesting a significant role of this particular isoform in human physiology.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    ‘That Time of the Month’ – Investigating the Influence of the Menstrual Cycle and Oral Contraceptives on the Brain Using Magnetic Resonance Imaging

    Verena SchusterAndreas Jansen
    10页
    查看更多>>摘要：The stereotypic and oversimplified relationship between female sex hormones and undesirable behavior dates to the earliest days of human society, as already the ancient Greek word for the uterus, “hystera” indicated an aversive connection. Remaining and evolving throughout the centuries, transcending across cultures and various aspects of everyday life, its perception was only recently reframed. Contemporarily, the complex interaction of hormonal phases (i.?e., the menstrual cycle), hormonal medication (i.?e., oral contraceptives), women’s psychological well-being, and behavior is the subject of multifaceted and more reflected discussions. A driving force of this ongoing paradigm shift was the introduction of this highly interesting and important topic into the realm of scientific research. This refers to neuroscientific research as it enables a multimodal approach combining aspects of physiology, medicine, and psychology. Here a growing body of literature points towards significant alterations of both brain function, such as lateralization of cognitive functions, and structure, such as gray matter concentrations, due to fluctuations and changes in hormonal levels. This especially concerns female sex hormones. However, the more research is conducted within this field, the less reliable these observations and derived insights appear. This may be due to two particular factors: measurement inconsistencies and diverse hormonal phases accompanied by interindividual differences. The first factor refers to the prominent unreliability of one of the primarily utilized neuroscientific research instruments: functional magnetic resonance imaging (fMRI). This unreliability is seemingly present in paradigms and analyses, and their interplay, and is additionally affected by the second factor. In more detail, hormonal phases and levels further influence neuroscientific results obtained through fMRI as outcomes vary drastically across different cycle phases and medication. This resulting vast uncertainty thus tremendously hinders the further advancement of our understanding of how female sex hormones might alter brain structure and function and, ultimately, behavior. This review summarizes parts of the current state of research and outlines the essential requirements to further investigate and understand the female brain’s underlying physiological and anatomical features.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    New Paradigms for Familiar Diseases: Lessons Learned on Circulatory Bacterial Signatures in Cardiometabolic Diseases

    Rima ChakarounLucas MassierNiculina MusatPeter Kovacs...
    14页
    查看更多>>摘要：Despite the strongly accumulating evidence for microbial signatures in metabolic tissues, including the blood, suggesting a novel paradigm for metabolic disease development, the notion of a core blood bacterial signature in health and disease remains a contentious concept. Recent studies clearly demonstrate that under a strict contamination-free environment, methods such as 16?S rRNA gene sequencing, fluorescence in-situ hybridization, transmission electron microscopy, and several more, allied with advanced bioinformatics tools, allow unambiguous detection and quantification of bacteria and bacterial DNA in human tissues. Bacterial load and compositional changes in the blood have been reported for numerous disease states, suggesting that bacteria and their components may partially induce systemic inflammation in cardiometabolic disease. This concept has been so far primarily based on measurements of surrogate parameters. It is now highly desirable to translate the current knowledge into diagnostic, prognostic, and therapeutic approaches. This review addresses the potential clinical relevance of a blood bacterial signature pertinent to cardiometabolic diseases and outcomes and new avenues for translational approaches. It discusses pitfalls related to research in low bacterial biomass while proposing mitigation strategies for future research and application approaches.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy

    Tine M. HansenJens B. Fr?kj?rDinesh SelvarajahJanusiya A. Muthulingam...
    8页
    查看更多>>摘要：Objective Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy.Methods 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored.Results In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume.Conclusions In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Impact of Smoking, Obesity and Maternal Diabetes on SHBG Levels in Newborns

    Banu Kucukemre AydinBeril YasaJoseph P. MooreCenk Yasa...
    8页
    查看更多>>摘要：Background Low levels of SHBG have become a marker for insulin resistance and diabetes. Babies born to mothers who are obese, have diabetes, or smoke during pregnancy are at greater risk of developing obesity and diabetes later in life.Aims To examine the impact of maternal obesity, diabetes and smoking on SHBG levels in newborns.Study design This cross-sectional study is part of an ongoing multicenter, longitudinal study.Subjects 98 healthy newborns and their parents, including 16 mothers with diabetes and 31 mothers with a smoking history.Outcome measures Cord blood and second day venipuncture samples were collected for measurement of SHBG and insulin.Results Babies born to mothers with diabetes had lower SHBG levels in cord blood [14.0 (8.9–20.4) vs. 19.6 (14.9–25.1)?nmol/L; p=0.011] and on day 2 [18.8 (12.6–21.2) vs. 22.9 (17.1–29.1)?nmol/L; p=0.015] than controls. Maternal diabetes remained negatively associated with SHBG levels in cord blood (p=0.02) and on day 2 (p=0.04) when adjusted for mothers’ age, smoking status, pre-pregnancy weight and weight gain during pregnancy. SHBG levels in cord blood and day 2 samples were similar in babies born to mothers who were overweight-obese but not diabetic vs. normal weight, or were smokers when compared to non-smokers.Conclusions: SHBG levels are lower in newborns born to mothers with diabetes than without diabetes, and may be a marker for babies’ life-long risk for abnormal metabolic health. On the other hand, the adverse effects of tobacco smoke on the fetus do not appear to directly influence SHBG levels.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Choice of Continuous Glucose Monitoring Systems May Affect Metrics: Clinically Relevant Differences in Times in Ranges

    Guido FreckmannStefan PleusSebastian SchauerManuela Link...
    8页
    查看更多>>摘要：Background Continuous glucose monitoring-derived parameters are becoming increasingly important in the treatment of people with diabetes. The aim of this study was to assess whether these parameters, as calculated from different continuous glucose monitoring systems worn in parallel, are comparable. In addition, clinical relevance of differences was investigated.Methods A total of 24 subjects wore a FreeStyle Libre (A) and a Dexcom G5 (B) sensor in parallel for 7 days. Mean glucose, coefficient of variation, glucose management indicator and time spent in different glucose ranges were calculated for each system. Pairwise differences between the two different continuous glucose monitoring systems were computed for these metrics.Results On average, the two CGM systems indicated an identical time in range (67.9±10.2 vs. 67.9±11.5%) and a similar coefficient of variation; both categorized as unstable (38.1±5.9 vs. 36.0±4.8%). In contrast, the mean time spent below and above range, as well as the individual times spent below, in and above range differed substantially. System A indicated about twice the time spent below range than system B (7.7±7.2 vs. 3.8±2.7%, p=0.003). This could have led to different therapy recommendations in approximately half of the subjects.Discussion The differences in metrics found between the two continuous glucose monitoring systems may result in different therapy recommendations. In order to make adequate clinical decisions, measurement performance of CGM systems should be standardized and all available information, including the HbA1c, should be utilized.
      原文链接:
    • NSTL
    • Thieme Medical Publishers