显示样式:     当前分类: 医药    当前期刊: Nature Reviews Endocrinology    加入关注    导出
我的关注
我的收藏
您暂时未登录!
登录
  • Diabetes: New marker to predict risk of T2DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    David Holmes

    Diabetes: New marker to predict risk of T2DM Nature Reviews Endocrinology, Published online: 22 September 2017; doi:10.1038/nrendo.2017.128

    更新日期:2017-09-22
  • Endocrine disruptors: Flame retardants and increased risk of thyroid cancer
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Bilal B. Mughal, Barbara A. Demeneix

    Endocrine disruptors: Flame retardants and increased risk of thyroid cancer Nature Reviews Endocrinology, Published online: 22 September 2017; doi:10.1038/nrendo.2017.123 Household dust contaminated with common flame retardants used in everyday household items has been found to be associated with increased risk of developing smaller, as well as more aggressive forms of papillary thyroid cancer in humans. These findings emphasize the need to consider the exposome when evaluating the increased incidence of thyroid cancer.

    更新日期:2017-09-22
  • Metabolism: Ketogenic diet rewires circadian clock
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Claire Greenhill

    Metabolism: Ketogenic diet rewires circadian clock Nature Reviews Endocrinology, Published online: 22 September 2017; doi:10.1038/nrendo.2017.129

    更新日期:2017-09-22
  • Transplantation: CXCL10 linked to poor outcomes
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    David Holmes

    Transplantation: CXCL10 linked to poor outcomes Nature Reviews Endocrinology, Published online: 15 September 2017; doi:10.1038/nrendo.2017.126

    更新日期:2017-09-15
  • Surgery: Postprandial hypoglycaemia following bariatric surgery
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Alan Morris

    Surgery: Postprandial hypoglycaemia following bariatric surgery Nature Reviews Endocrinology, Published online: 15 September 2017; doi:10.1038/nrendo.2017.125

    更新日期:2017-09-15
  • Diabetes: Cardiovascular benefits of metformin in T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Janet K. Snell-Bergeon

    Diabetes: Cardiovascular benefits of metformin in T1DM Nature Reviews Endocrinology, Published online: 12 September 2017; doi:10.1038/nrendo.2017.116 Results from the Reducing with Metformin Vascular Adverse Lesions (REMOVAL) study show for the first time that metformin has a cardiovascular benefit in patients with type 1 diabetes mellitus (T1DM), although the benefit was limited to tertiary outcomes and was modest. Additional measures are therefore needed to reduce cardiovascular disease in patients with T1DM.

    更新日期:2017-09-13
  • Diabetes: The diabetic brain
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    John E. Morley

    Diabetes: The diabetic brain Nature Reviews Endocrinology, Published online: 12 September 2017; doi:10.1038/nrendo.2017.111 Dementia is a complication associated with diabetes mellitus. Evidence suggests that patients with diabetes mellitus who have dementia have a unique form of the disease, albeit with similarities to vascular dementia. A recent study by Juraj Secnik and colleagues confirms this suggestion and provides insights into the clinical characteristics and treatment of the disorder.

    更新日期:2017-09-13
  • Diabetes: Risk of T2DM in children — influence of sleep duration
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-01
    Claire Greenhill

    In adults, short sleep duration is known to be associated with an increased risk of type 2 diabetes mellitus (T2DM), but whether this association is also present in children is unclear. A new study published in Pediatrics has begun to answer this question.The

    更新日期:2017-09-12
  • Obesity: New insights into BAT activity
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-11
    Alan Morris

    In humans, brown adipose tissue (BAT) activity can contribute to changes in energy expenditure and increased levels of BAT can improve insulin sensitivity. The overall effect of BAT on human metabolism, however, remains contested. Now, new data show that previous studies could have underestimated the

    更新日期:2017-09-12
  • Diabetes: Systemic effects of metformin revealed
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-18
    Alan Morris

    Metformin is widely prescribed to treat patients with type 2 diabetes mellitus, but the whole-body systemic responses to the drug remain unclear. Now, new research conducted by Michaela Reagan and colleagues reveals the effects of metformin in lean and obese mice on bone, bone marrow

    更新日期:2017-09-12
  • Thyroid function: Thyroid hypofunction in pregnancy
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-11
    Claire Greenhill

    The 2017 Guidelines of the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and postpartum recommend that pregnant women requiring treatment for thyroid dysfunction are identified using a case-finding method that takes account of their history of thyroid dysfunction

    更新日期:2017-09-12
  • Diabetes: Falling insulin requirements — a red flag for pre-eclampsia
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-29
    David Holmes

    Women with pre-existing diabetes mellitus whose insulin requirements fall during pregnancy have a markedly increased risk of developing pre-eclampsia and other adverse obstetric outcomes, according to new research. As the fall in insulin requirement seems to precede the onset of pre-eclampsia, clinicians should be alert

    更新日期:2017-09-12
  • Gut microbiota: Gas-induced GLP1 release
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-18
    David Holmes

    New research shows that hydrogen sulphide (H2S), a microbial gas produced in the colon by sulphate-reducing bacteria (SRB), can directly stimulate the release of glucagon-like peptide 1 (GLP1; an incretin hormone involved in glucose homeostasis and appetite regulation) from enteroendocrine L cells in

    更新日期:2017-09-12
  • Diabetes: Peripheral Aβ linked to pathogenesis of T2DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-01
    Alan Morris

    Epidemiological studies suggest that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing Alzheimer disease, but the mechanistic underpinnings of this relationship remain unclear. In a new study, Nadeeja Wijesekara and colleagues investigated the link between these two diseases in a

    更新日期:2017-09-12
  • Therapy: Immunotherapy advance for T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-29
    Claire Greenhill

    Therapies that modulate the immune system of patients with type 1 diabetes mellitus (T1DM) have been the focus of much research in the past few years; however, no therapy that is both efficacious and safe has been identified so far. New research published in Science

    更新日期:2017-09-12
  • Obesity: Obesity and cardiometabolic disease — more than meets the eye
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-01
    Stella Aslibekyan, W. Timothy Garvey

    Whether obesity is a cause of type 2 diabetes mellitus and coronary heart disease or a shared risk factor has been an enduring subject of debate. Lyall and colleagues have used Mendelian randomization to conclude that there is a causal relationship between obesity and cardiometabolic disease. However, the analyses fail key inherent assumptions. The article does not negate a large body of data indicating that insulin resistance is the primary mechanism driving the progression of cardiometabolic disease.

    更新日期:2017-09-12
  • Diabetes: Insulin pumps after injections and CGM in T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-18
    John C. Pickup

    A recent randomized controlled trial has shown that patients with type 1 diabetes mellitus who are treated with multiple daily insulin injections and continuous glucose monitoring (CGM) enjoy a further improvement in glycaemic control when switched to insulin pump therapy with CGM. However, some increase in biochemical hypoglycaemia was evident with pump treatment.

    更新日期:2017-09-12
  • Diabetes: Cardiovascular benefits of metformin in T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-12
    Janet K. Snell-Bergeon

    Results from the Reducing with Metformin Vascular Adverse Lesions (REMOVAL) study show for the first time that metformin has a cardiovascular benefit in patients with type 1 diabetes mellitus (T1DM), although the benefit was limited to tertiary outcomes and was modest. Additional measures are therefore needed to reduce cardiovascular disease in patients with T1DM.

    更新日期:2017-09-12
  • Regulation of hepatic glucose metabolism in health and disease
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-21
    Max C. Petersen, Daniel F. Vatner, Gerald I. Shulman

    The liver is crucial for the maintenance of normal glucose homeostasis — it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.

    更新日期:2017-09-12
  • Diabetes: The diabetic brain
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-12
    John E. Morley

    Dementia is a complication associated with diabetes mellitus. Evidence suggests that patients with diabetes mellitus who have dementia have a unique form of the disease, albeit with similarities to vascular dementia. A recent study by Juraj Secnik and colleagues confirms this suggestion and provides insights into the clinical characteristics and treatment of the disorder.

    更新日期:2017-09-12
  • Central hypothyroidism — a neglected thyroid disorder
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-05-26
    Paolo Beck-Peccoz, Giulia Rodari, Claudia Giavoli, Andrea Lania

    Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T4 or TSH measurements; routine utilization of total T4 or T3 measurements; concurrent systemic illness that is characterized by low levels of free T4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T4, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T4. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

    更新日期:2017-09-12
  • FGF1 — a new weapon to control type 2 diabetes mellitus
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-06-30
    Emanuel Gasser, Christopher P. Moutos, Michael Downes, Ronald M. Evans

    A hypercaloric diet combined with a sedentary lifestyle is a major risk factor for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and associated comorbidities. Standard treatment for T2DM begins with lifestyle modification, and includes oral medications and insulin therapy to compensate for progressive β-cell failure. However, current pharmaceutical options for T2DM are limited in that they do not maintain stable, durable glucose control without the need for treatment intensification. Furthermore, each medication is associated with adverse effects, which range from hypoglycaemia to weight gain or bone loss. Unexpectedly, fibroblast growth factor 1 (FGF1) and its low mitogenic variants have emerged as potentially safe candidates for restoring euglycaemia, without causing overt adverse effects. In particular, a single peripheral injection of FGF1 can lower glucose to normal levels within hours, without the risk of hypoglycaemia. Similarly, a single intracerebroventricular injection of FGF1 can induce long-lasting remission of the diabetic phenotype. This Review discusses potential mechanisms by which centrally administered FGF1 improves central glucose-sensing and peripheral glucose uptake in a sustained manner. Specifically, we explore the potential crosstalk between FGF1 and glucose-sensing neuronal circuits, hypothalamic neural stem cells and synaptic plasticity. Finally, we highlight therapeutic considerations of FGF1 and compare its metabolic actions with FGF15 (rodents), FGF19 (humans) and FGF21.

    更新日期:2017-09-12
  • Thyroid disease in pregnancy: new insights in diagnosis and clinical management
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-04
    Tim I. M. Korevaar, Marco Medici, Theo J. Visser, Robin P. Peeters

    Adequate thyroid hormone availability is important for an uncomplicated pregnancy and optimal fetal growth and development. Overt thyroid disease is associated with a wide range of adverse obstetric and child development outcomes. An increasing number of studies now indicate that milder forms of thyroid dysfunction are also associated with these adverse pregnancy outcomes. The definitions of both overt and subclinical thyroid dysfunction have changed considerably over the past few years, as new data indicate that the commonly used fixed upper limits of 2.5 mU/l or 3.0 mU/l for thyroid-stimulating hormone (TSH) are too low to define an abnormal thyroid function. Furthermore, some studies now show that the reference ranges are not necessarily the best cut-off for identifying pregnancies at high risk of adverse outcomes. In addition, data suggest that thyroid peroxidase autoantibody positivity and high or low concentrations of human chorionic gonadotropin seem to have a more prominent role in the interpretation of thyroid dysfunction than previously thought. Data on the effects of thyroid disease treatment are lacking, but some studies indicate that clinicians should be aware of the potential for overtreatment with levothyroxine. Here, we put studies from the past decade on reference ranges for TSH, determinants of thyroid dysfunction, risks of adverse outcomes and options for treatment into perspective. In addition, we provide an overview of the current views on thyroid physiology during pregnancy and discuss strategies to identify high-risk individuals who might benefit from levothyroxine treatment.

    更新日期:2017-09-12
  • Chronic endocrine consequences of traumatic brain injury — what is the evidence?
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-08
    Marianne Klose, Ulla Feldt-Rasmussen

    Chronic endocrine consequences of traumatic brain injury — what is the evidence? Nature Reviews Endocrinology, Published online: 8 September 2017; doi:10.1038/nrendo.2017.103 In this Opinion article, Klose and Feldt-Rasmussen posit that the true risk and disease burden of hypopituitarism after traumatic brain injury might have been overestimated in recent years. Possible reasons for this overestimation are discussed, along with current recommendations for diagnosing and treating the condition.

    更新日期:2017-09-10
  • Adult-onset autoimmune diabetes: current knowledge and implications for management
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-08
    Raffaella Buzzetti, Simona Zampetti, Ernesto Maddaloni

    Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.

    更新日期:2017-09-10
  • Bone diseases: New hope for old bones
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    David Holmes

    Bone diseases: New hope for old bones Nature Reviews Endocrinology, Published online: 8 September 2017; doi:10.1038/nrendo.2017.121

    更新日期:2017-09-10
  • Primary hyperparathyroidism
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-08
    Marcella D. Walker, Shonni J. Silverberg

    In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a common endocrine disorder that is characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Most often, the presentation of PHPT is asymptomatic in regions of the world where serum levels of calcium are routinely measured. In addition to mild hypercalcaemia, PHPT can manifest with osteoporosis and hypercalciuria as well as with vertebral fractures and nephrolithiasis, both of which can be asymptomatic. Other clinical forms of PHPT, such as classical disease and normocalcaemic PHPT, are less common. Parathyroidectomy, the only curative treatment for PHPT, is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. Various medical therapies can increase BMD or reduce serum levels of calcium, but no single drug can do both. More data are needed regarding the neuropsychological manifestations of PHPT and the pathogenetic mechanisms leading to sporadic PHPT, as well as on risk factors for complications of the disorder. Future work that advances our knowledge in these areas will improve the management of the disorder.

    更新日期:2017-09-10
  • Obesity: Role for creatine metabolism in energy expenditure
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Claire Greenhill

    Obesity: Role for creatine metabolism in energy expenditure Nature Reviews Endocrinology, Published online: 8 September 2017; doi:10.1038/nrendo.2017.120

    更新日期:2017-09-10
  • Diabetes: Insulin pumps after injections and CGM in T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-18
    John C. Pickup

    A recent randomized controlled trial has shown that patients with type 1 diabetes mellitus who are treated with multiple daily insulin injections and continuous glucose monitoring (CGM) enjoy a further improvement in glycaemic control when switched to insulin pump therapy with CGM. However, some increase in biochemical hypoglycaemia was evident with pump treatment.

    更新日期:2017-09-06
  • Obesity: Obesity and cardiometabolic disease — more than meets the eye
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-01
    Stella Aslibekyan, W. Timothy Garvey

    Whether obesity is a cause of type 2 diabetes mellitus and coronary heart disease or a shared risk factor has been an enduring subject of debate. Lyall and colleagues have used Mendelian randomization to conclude that there is a causal relationship between obesity and cardiometabolic disease. However, the analyses fail key inherent assumptions. The article does not negate a large body of data indicating that insulin resistance is the primary mechanism driving the progression of cardiometabolic disease.

    更新日期:2017-09-06
  • Central hypothyroidism — a neglected thyroid disorder
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-05-26
    Paolo Beck-Peccoz, Giulia Rodari, Claudia Giavoli, Andrea Lania

    Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T4 or TSH measurements; routine utilization of total T4 or T3 measurements; concurrent systemic illness that is characterized by low levels of free T4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T4, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T4. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

    更新日期:2017-09-06
  • Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    Eleonora Molinaro, Cristina Romei, Agnese Biagini, Elena Sabini, Laura Agate, Salvatore Mazzeo, Gabriele Materazzi, Stefano Sellari-Franceschini, Alessandro Ribechini, Liborio Torregrossa, Fulvio Basolo, Paolo Vitti, Rossella Elisei

    Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1–2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed.

    更新日期:2017-09-06
  • FGF1 — a new weapon to control type 2 diabetes mellitus
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-06-30
    Emanuel Gasser, Christopher P. Moutos, Michael Downes, Ronald M. Evans

    A hypercaloric diet combined with a sedentary lifestyle is a major risk factor for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and associated comorbidities. Standard treatment for T2DM begins with lifestyle modification, and includes oral medications and insulin therapy to compensate for progressive β-cell failure. However, current pharmaceutical options for T2DM are limited in that they do not maintain stable, durable glucose control without the need for treatment intensification. Furthermore, each medication is associated with adverse effects, which range from hypoglycaemia to weight gain or bone loss. Unexpectedly, fibroblast growth factor 1 (FGF1) and its low mitogenic variants have emerged as potentially safe candidates for restoring euglycaemia, without causing overt adverse effects. In particular, a single peripheral injection of FGF1 can lower glucose to normal levels within hours, without the risk of hypoglycaemia. Similarly, a single intracerebroventricular injection of FGF1 can induce long-lasting remission of the diabetic phenotype. This Review discusses potential mechanisms by which centrally administered FGF1 improves central glucose-sensing and peripheral glucose uptake in a sustained manner. Specifically, we explore the potential crosstalk between FGF1 and glucose-sensing neuronal circuits, hypothalamic neural stem cells and synaptic plasticity. Finally, we highlight therapeutic considerations of FGF1 and compare its metabolic actions with FGF15 (rodents), FGF19 (humans) and FGF21.

    更新日期:2017-09-06
  • Regulation of hepatic glucose metabolism in health and disease
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-21
    Max C. Petersen, Daniel F. Vatner, Gerald I. Shulman

    The liver is crucial for the maintenance of normal glucose homeostasis — it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.

    更新日期:2017-09-06
  • Adapting to obesity with adipose tissue inflammation
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-11
    Shannon M. Reilly, Alan R. Saltiel

    Adipose tissue not only has an important role in the storage of excess nutrients but also senses nutrient status and regulates energy mobilization. An overall positive energy balance is associated with overnutrition and leads to excessive accumulation of fat in adipocytes. These cells respond by initiating an inflammatory response that, although maladaptive in the long run, might initially be a physiological response to the stresses obesity places on adipose tissue. In this Review, we characterize adipose tissue inflammation and review the current knowledge of what triggers obesity-associated inflammation in adipose tissue. We examine the connection between adipose tissue inflammation and the development of insulin resistance and catecholamine resistance and discuss the ensuing state of metabolic inflexibility. Finally, we review the current and potential new anti-inflammatory treatments for obesity-associated metabolic disease.

    更新日期:2017-09-06
  • SREBP-regulated lipid metabolism: convergent physiology — divergent pathophysiology
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-29
    Hitoshi Shimano, Ryuichiro Sato

    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

    更新日期:2017-09-06
  • Thyroid disease in pregnancy: new insights in diagnosis and clinical management
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-04
    Tim I. M. Korevaar, Marco Medici, Theo J. Visser, Robin P. Peeters

    Adequate thyroid hormone availability is important for an uncomplicated pregnancy and optimal fetal growth and development. Overt thyroid disease is associated with a wide range of adverse obstetric and child development outcomes. An increasing number of studies now indicate that milder forms of thyroid dysfunction are also associated with these adverse pregnancy outcomes. The definitions of both overt and subclinical thyroid dysfunction have changed considerably over the past few years, as new data indicate that the commonly used fixed upper limits of 2.5 mU/l or 3.0 mU/l for thyroid-stimulating hormone (TSH) are too low to define an abnormal thyroid function. Furthermore, some studies now show that the reference ranges are not necessarily the best cut-off for identifying pregnancies at high risk of adverse outcomes. In addition, data suggest that thyroid peroxidase autoantibody positivity and high or low concentrations of human chorionic gonadotropin seem to have a more prominent role in the interpretation of thyroid dysfunction than previously thought. Data on the effects of thyroid disease treatment are lacking, but some studies indicate that clinicians should be aware of the potential for overtreatment with levothyroxine. Here, we put studies from the past decade on reference ranges for TSH, determinants of thyroid dysfunction, risks of adverse outcomes and options for treatment into perspective. In addition, we provide an overview of the current views on thyroid physiology during pregnancy and discuss strategies to identify high-risk individuals who might benefit from levothyroxine treatment.

    更新日期:2017-09-06
  • Genomic and epigenomic mechanisms of glucocorticoids in the brain
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-09-01
    Jason D. Gray, Joshua F. Kogan, Jordan Marrocco, Bruce S. McEwen

    Following the discovery of glucocorticoid receptors in the hippocampus and other brain regions, research has focused on understanding the effects of glucocorticoids in the brain and their role in regulating emotion and cognition. Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Allostatic overload, which can occur during chronic stress, can reshape the hypothalamic–pituitary–adrenal axis through epigenetic modification of genes in the hippocampus, hypothalamus and other stress-responsive brain regions. Glucocorticoids exert their effects on the brain through genomic mechanisms that involve both glucocorticoid receptors and mineralocorticoid receptors directly binding to DNA, as well as by non-genomic mechanisms. Furthermore, glucocorticoids synergize both genomically and non-genomically with neurotransmitters, neurotrophic factors, sex hormones and other stress mediators to shape an organism's present and future responses to a stressful environment. Here, we discuss the mechanisms of glucocorticoid action in the brain and review how glucocorticoids interact with stress mediators in the context of allostasis, allostatic load and stress-induced neuroplasticity.

    更新日期:2017-09-06
  • 'Omics' and endocrine-disrupting chemicals — new paths forward
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    Carmen Messerlian, Rosie M. Martinez, Russ Hauser, Andrea A. Baccarelli

    The emerging field of omics has the potential to advance and strengthen research into endocrine-disrupting chemicals (EDCs). In this Opinion article, Andrea Baccarelli and colleagues discuss the potential of using omics technologies — both established and developing — to characterize present and past EDC exposures and predict risk of developing EDC-related diseases.

    更新日期:2017-09-06
  • Diabetes: Risk of T2DM in children — influence of sleep duration
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Claire Greenhill

    Diabetes: Risk of T2DM in children — influence of sleep duration Nature Reviews Endocrinology, Published online: 1 September 2017; doi:10.1038/nrendo.2017.117

    更新日期:2017-09-06
  • Diabetes: Peripheral Aβ linked to pathogenesis of T2DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Alan Morris

    Diabetes: Peripheral Aβ linked to pathogenesis of T2DM Nature Reviews Endocrinology, Published online: 1 September 2017; doi:10.1038/nrendo.2017.118

    更新日期:2017-09-06
  • Therapy: Immunotherapy advance for T1DM
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Claire Greenhill

    Therapy: Immunotherapy advance for T1DM Nature Reviews Endocrinology, Published online: 29 August 2017; doi:10.1038/nrendo.2017.113

    更新日期:2017-09-06
  • Diabetes: Falling insulin requirements — a red flag for pre-eclampsia
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    David Holmes

    Diabetes: Falling insulin requirements — a red flag for pre-eclampsia Nature Reviews Endocrinology, Published online: 29 August 2017; doi:10.1038/nrendo.2017.114

    更新日期:2017-09-06
  • Diabetes: Systemic effects of metformin revealed
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 
    Alan Morris

    Diabetes: Systemic effects of metformin revealed Nature Reviews Endocrinology, Published online: 18 August 2017; doi:10.1038/nrendo.2017.109

    更新日期:2017-09-06
  • β-Cell mass versus function in type 1 diabetes mellitus: truth or dare?
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-07
    Teresa Rodriguez-Calvo, Mark Atkinson, Matthias von Herrath

    In a recent article by Mikael Knip (Loss of β-cell mass — an acute event before T1DM presentation? Nat. Rev. Endocrinol. 13, 253–254 (2017)), a series of issues were raised with respect to our article that we would like to

    更新日期:2017-08-24
  • Obesity: Olfactory senses linked to metabolism
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    Alan Morris

    New research demonstrates that the perception of food via the olfactory senses can alter energy homeostasis in mice. Andrew Dillin, Jens Brüning (co-corresponding authors) and colleagues found that animals lacking olfactory sensory perception ate the same amount as animals that could smell, but did not

    更新日期:2017-08-24
  • Type 1 diabetes mellitus is a heterogeneous disease
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-07
    Mikael Knip

    I would like to thank Teresa Rodriguez-Calvo, Mark Atkinson and Matthias von Herrath for their correspondence on my News & Views article (Loss of β-cell mass — an acute event before T1DM presentation? Nat. Rev. Endocrinol. 13, 253–254 (2017)), which raised

    更新日期:2017-08-24
  • Targeted therapies: Lenvatinib SELECTs survival benefit
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    Lisa Hutchinson

    Until the past 4 years, no treatment option existed for patients with refractory differentiated thyroid cancer, who were treated routinely with supportive care. The first drug to be approved for these patients by the FDA was sorafenib in 2013, followed by lenvatinib in 2015 —

    更新日期:2017-08-24
  • Liver: Paradigm shift in the immunopathogenesis of NAFLD
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    David Holmes

    In states of obesity, the development and fibrotic progression of nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH) to cirrhosis has been proposed to stem from chronic, low-level type 1 inflammation in adipose tissue. However, new research challenges this view by showing instead that

    更新日期:2017-08-24
  • Gut microbiota: Link between the gut and adipose tissues
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-07
    Alan Morris

    New research suggests that the hepatic enzyme flavin-containing monooxygenase 3 (FMO3) is associated with the beiging of white adipose tissue in mice and humans.Brown adipose tissue is important for energy expenditure in the form of thermogenesis. Beiging, which is the formation of metabolically active

    更新日期:2017-08-24
  • Obesity: Gut microbiome and serum metabolome changes
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-07
    Claire Greenhill

    Although the gut microbiota is thought to be involved in the development of obesity, the exact nature of this relationship is unclear. New research in a cohort of Han Chinese individuals has revealed specific alterations in the gut microbial species present in people with obesity,

    更新日期:2017-08-24
  • Neuroendocrinology: Integrated stress response linked to TBI
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-28
    Alan Morris

    Integrated stress response inhibitor (ISRIB), a potent and selective small-molecule inhibitor of the integrated stress response, can ameliorate cognitive deficits in mouse models of traumatic brain injury (TBI), according to new research. The findings, reported by Susanna Rosi and colleagues, are the first to show

    更新日期:2017-08-24
  • Growth and development: Dwarfism linked to hypertension treatment
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-21
    David Holmes

    Treatment of female mice with an α1-adrenergic antagonist during pregnancy results in dwarfism and insulin resistance in male offspring, according to new findings published in Molecular Metabolism. “As combined α1/β-adrenergic blockers are currently recommended as first-line and second-line treatments for gestational hypertension, the findings

    更新日期:2017-08-24
  • Neuroendocrinology: Central insulin regulates eating behaviour
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-04
    Claire Greenhill

    Previous work in animal models has suggested that insulin could be involved in hedonic eating via actions on the dopaminergic reward system. A new study, published in Nature Communications, demonstrates that central insulin has similar effects in humans.“These recent animal data are fascinating,

    更新日期:2017-08-24
  • Bone cancer: Is the osteosarcoma genome targetable?
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-04
    Sharon A. Savage, Lisa Mirabello

    The osteosarcoma genome has long been known to be complex, with few common features between tumours. However, a growing number of somatic genome studies, including a recent study by Behjati et al., have identified common themes in subsets of these cancers. The data suggest that subsets of somatic signatures could be therapeutically tractable targets.

    更新日期:2017-08-24
  • Obesity: Maternal obesity and congenital anomalies — risk and diagnosis
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-08-04
    Jodie M. Dodd, Clare L. Whitehead

    A new population-based observational cohort study involving more than 1.2 million live births highlights the increased risk of congenital anomalies with increasing degrees of maternal overweight and obesity. However, by only considering data on live-born infants, the full impact of maternal overweight and obesity on this aspect of reproductive and child health is underestimated.

    更新日期:2017-08-24
  • Cardiovascular endocrinology: Is ANGPTL3 the next PCSK9?
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-07-14
    Kiran Musunuru, Sekar Kathiresan

    Recent reports suggest that molecular therapies targeting ANGPTL3 and its encoded protein angiopoietin-like protein 3 have clinical potential comparable to therapies targeting PCSK9 and its encoded protein proprotein convertase subtilisin/kexin type 9. By mainly affecting triglyceride-rich lipoproteins, ANGPTL3 inhibition might prove complementary to LDL cholesterol lowering with PCSK9 blockade.

    更新日期:2017-08-24
  • Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-06-09
    Ruth C. R. Meex, Matthew J. Watt

    Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ~70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.

    更新日期:2017-08-24
  • The gentle art of saying NO: how nitric oxide gets things done in the hypothalamus
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-06-16
    Konstantina Chachlaki, John Garthwaite, Vincent Prevot

    The chemical signalling molecule nitric oxide (NO), which freely diffuses through aqueous and lipid environments, subserves an array of functions in the mammalian central nervous system, such as the regulation of synaptic plasticity, blood flow and neurohormone secretion. In this Review, we consider the cellular and molecular mechanisms by which NO evokes short-term and long-term changes in neuronal activity. We also highlight recent studies showing that discrete populations of neurons that synthesize NO in the hypothalamus constitute integrative systems that support life by relaying metabolic and gonadal signals to the neuroendocrine brain, and thus gate the onset of puberty and adult fertility. The putative involvement and therapeutic potential of NO in the pathophysiology of brain diseases, for which hormonal imbalances during postnatal development could be risk factors, is also discussed.

    更新日期:2017-08-24
  • Endocrine-disrupting chemicals and the regulation of energy balance
    Nat. Rev. Endocrinol. (IF 18.318) Pub Date : 2017-05-19
    Angel Nadal, Ivan Quesada, Eva Tudurí, Rubén Nogueiras, Paloma Alonso-Magdalena

    Energy balance involves the adjustment of food intake, energy expenditure and body fat reserves through homeostatic pathways. These pathways include a multitude of biochemical reactions, as well as hormonal cues. Dysfunction of this homeostatic control system results in common metabolism-related pathologies, which include obesity and type 2 diabetes mellitus. Metabolism-disrupting chemicals (MDCs) are a particular class of endocrine-disrupting chemicals that affect energy homeostasis. MDCs affect multiple endocrine mechanisms and thus different cell types that are implicated in metabolic control. MDCs affect gene expression and the biosynthesis of key enzymes, hormones and adipokines that are essential for controlling energy homeostasis. This multifaceted spectrum of actions precludes compensatory responses and favours metabolic disorders. Herein, we review the main mechanisms used by MDCs to alter energy balance. This work should help to identify new MDCs, as well as novel targets of their action.

    更新日期:2017-08-24
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
所有期刊列表A-Z