Browse

You are looking at 61 - 70 of 4,410 items for

  • Refine by access: Content accessible to me x
Clear All
Chau Thien Tay Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
Department of Endocrinology and Diabetes, Monash Health, Victoria, Australia

Search for other papers by Chau Thien Tay in
Google Scholar
PubMed
Close
,
Rhonda Garrad Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia

Search for other papers by Rhonda Garrad in
Google Scholar
PubMed
Close
,
Aya Mousa Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia

Search for other papers by Aya Mousa in
Google Scholar
PubMed
Close
,
Mahnaz Bahri Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia

Search for other papers by Mahnaz Bahri in
Google Scholar
PubMed
Close
,
Anju Joham Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
Department of Endocrinology and Diabetes, Monash Health, Victoria, Australia

Search for other papers by Anju Joham in
Google Scholar
PubMed
Close
, and
Helena Teede Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
Department of Endocrinology and Diabetes, Monash Health, Victoria, Australia

Search for other papers by Helena Teede in
Google Scholar
PubMed
Close

Polycystic ovary syndrome (PCOS) affects 8–13% of reproductive-aged women, impacts biopsychosocial factors and creates a significant health-related economic burden across the reproductive, metabolic and psychological spectrum of complications. Despite being a heterogenous condition, recent genomic studies indicate that PCOS, regardless of diagnostic criteria and clinical features, shares similar underlying biologic mechanisms. However, recent advances have shown that clinical reproductive and diagnostic features are poorly correlated to genotypes and do not represent true phenotypes. Until we have a better understanding of genetic and epigenetic influences on PCOS and long-term outcomes, targeted treatment is limited.

In the interim, a unified approach to integrate evidence, optimise management and guide future research in PCOS is necessary. This has motivated an international collaboration to develop an International Evidence-Based PCOS Guideline to improve health outcomes in women with PCOS. Dissemination and translation of the guideline into health policy and clinical practice are crucial steps to close the knowledge–-practice gap, guide future research and enhance positive impact on the health of women with PCOS.

Here, we review the (i) understanding of aetiology and genetics of PCOS; (ii) development and translation efforts of the 2018 International Evidence-based PCOS Guideline; (iii) current progress and plans for the guideline update, including the involvement of an early career researcher network to assist with evidence synthesis and (iv) the opportunity to target and guide future research for PCOS.

Free access
Renea A Taylor Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia
Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia

Search for other papers by Renea A Taylor in
Google Scholar
PubMed
Close
,
Mitchell G Lawrence Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia

Search for other papers by Mitchell G Lawrence in
Google Scholar
PubMed
Close
, and
Gail P Risbridger Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia

Search for other papers by Gail P Risbridger in
Google Scholar
PubMed
Close

There is longstanding interest in the role of androgens in the aetiology of prostate cancer, one of the most common malignancies worldwide. In this review, we reflect on the ways that knowledge of prostate development and hormone action have catalysed advances in the management of patients with prostate cancer. The use of hormone therapies to treat prostate cancer has changed significantly over time, including the emergence of androgen receptor signalling inhibitors (ARSI). These compounds have improved outcomes for patients with castration-resistant prostate cancer, which was once considered ‘androgen-independent’ but is clearly still driven by androgen receptor signalling in many cases. There is also a need for new therapies to manage neuroendocrine prostate cancer, which is not responsive to hormonal agents. One of the major gaps is understanding how treatment-induced neuroendocrine prostate cancer emerges and whether it can be re-sensitised to treatment. Patient-derived models, including patient-derived xenografts (PDXs), will be instrumental in facilitating future discoveries in these areas. Developments in the use of PDXs have been fostered by lessons from the field of endocrinology, such as the role of stroma and hormones in normal and developmental tissues. Thus, there is ongoing reciprocity between the discoveries in endocrinology and advances in prostate cancer research and treatment.

Free access
Bettina Geidl-Flueck Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland

Search for other papers by Bettina Geidl-Flueck in
Google Scholar
PubMed
Close
and
Philipp A Gerber Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland

Search for other papers by Philipp A Gerber in
Google Scholar
PubMed
Close

Despite the existence of numerous studies supporting a pathological link between fructose consumption and the development of the metabolic syndrome and its sequelae, such as non-alcoholic fatty liver disease (NAFLD), this link remains a contentious issue. With this article, we shed a light on the impact of sugar/fructose intake on hepatic de novo lipogenesis (DNL), an outcome parameter known to be dysregulated in subjects with type 2 diabetes and/or NAFLD. In this review, we present findings from human intervention studies using physiological doses of sugar as well as mechanistic animal studies. There is evidence from both human and animal studies that fructose is a more potent inducer of hepatic lipogenesis than glucose. This is most likely due to the liver’s prominent physiological role in fructose metabolism, which may be disrupted under pathological conditions by increased hepatic expression of fructolytic and lipogenic enzymes. Increased DNL may not only contribute to ectopic fat deposition (i.e. in the liver), but it may also impair several metabolic processes through DNL-related fatty acids (e.g. beta-cell function, insulin secretion, or insulin sensitivity).

Open access
Vicki Chen Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

Search for other papers by Vicki Chen in
Google Scholar
PubMed
Close
,
Gia V Shelp Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

Search for other papers by Gia V Shelp in
Google Scholar
PubMed
Close
,
Jacob L Schwartz Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

Search for other papers by Jacob L Schwartz in
Google Scholar
PubMed
Close
,
Niklas D J Aardema Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, Utah, United States

Search for other papers by Niklas D J Aardema in
Google Scholar
PubMed
Close
,
Madison L Bunnell Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, Utah, United States

Search for other papers by Madison L Bunnell in
Google Scholar
PubMed
Close
, and
Clara E Cho Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

Search for other papers by Clara E Cho in
Google Scholar
PubMed
Close

Micronutrients consumed in excess or imbalanced amounts during pregnancy may increase the risk of metabolic diseases in offspring, but the mechanisms underlying these effects are unknown. Serotonin (5-hydroxytryptamine, 5-HT), a multifunctional indoleamine in the brain and the gut, may have key roles in regulating metabolism. We investigated the effects of gestational micronutrient intakes on the central and peripheral serotonergic systems as modulators of the offspring's metabolic phenotypes. Pregnant Wistar rats were fed an AIN-93G diet with 1-fold recommended vitamins (RV), high 10-fold multivitamins (HV), high 10-fold folic acid with recommended choline (HFolRC), or high 10-fold folic acid with no choline (HFolNC). Male and female offspring were weaned to a high-fat RV diet for 12 weeks. We assessed the central function using the 5-HT2C receptor agonist, 1-(3-chlorophenyl)piperazine (mCPP), and found that male offspring from the HV- or HFolRC-fed dams were less responsive (P < 0.05) whereas female HFolRC offspring were more responsive to mCPP (P < 0.01) at 6 weeks post-weaning. Male and female offspring from the HV and HFolNC groups, and male HFolRC offspring had greater food intake (males P < 0.001; females P < 0.001) and weight gain (males P < 0.0001; females P < 0.0001), elevated colon 5-HT (males P < 0.01; females P < 0.001) and fasting glucose concentrations (males P < 0.01; females P < 0.01), as well as body composition toward obesity (males P < 0.01; females P < 0.01) at 12 weeks post-weaning. Colon 5-HT was correlated with fasting glucose concentrations (males R2=0.78, P < 0.0001; females R2=0.71, P < 0.0001). Overall, the serotonergic systems are sensitive to the composition of gestational micronutrients, with alterations consistent with metabolic disturbances in offspring.

Open access
Sy-Ying Leu Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC

Search for other papers by Sy-Ying Leu in
Google Scholar
PubMed
Close
,
Yi-Ling Tsang Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
Institute of Physiological Chemistry and Pathobiochemistry and Cells in Motion Interfaculty Centre, University of Münster, Münster, Germany

Search for other papers by Yi-Ling Tsang in
Google Scholar
PubMed
Close
,
Li-Chun Ho School of Medicine, I-Shou University, Kaohsiung, Taiwan, ROC
Division of General Medicine, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan, ROC

Search for other papers by Li-Chun Ho in
Google Scholar
PubMed
Close
,
Ching-Chun Yang Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Search for other papers by Ching-Chun Yang in
Google Scholar
PubMed
Close
,
Ai-Ning Shao Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Search for other papers by Ai-Ning Shao in
Google Scholar
PubMed
Close
,
Chia-Yu Chang Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Search for other papers by Chia-Yu Chang in
Google Scholar
PubMed
Close
,
Hui-Kuan Lin Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA

Search for other papers by Hui-Kuan Lin in
Google Scholar
PubMed
Close
,
Pei-Jane Tsai Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Search for other papers by Pei-Jane Tsai in
Google Scholar
PubMed
Close
,
Junne-Ming Sung Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC

Search for other papers by Junne-Ming Sung in
Google Scholar
PubMed
Close
, and
Yau-Sheng Tsai Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan, Taiwan, ROC

Search for other papers by Yau-Sheng Tsai in
Google Scholar
PubMed
Close

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an oligomeric complex that assembles in response to exogenous signals of pathogen infection and endogenous danger signals of non-microbial origin. When NLRP3 inflammasome assembly activates caspase-1, it promotes the maturation and release of the inflammatory cytokines interleukin-1B and IL-18. Aberrant activation of the NLRP3 inflammasome has been implicated in various diseases, including chronic inflammatory, metabolic, and cardiovascular diseases. The NLRP3 inflammasome can be activated through several principal mechanisms, including K+ efflux, lysosomal damage, and the production of mitochondrial reactive oxygen species. Interestingly, metabolic danger signals activate the NLRP3 inflammasome to induce metabolic diseases. NLRP3 contains three crucial domains: an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat domain. Protein–protein interactions act as a ‘pedal or brake’ to control the activation of the NLRP3 inflammasome. In this review, we present the mechanisms underlying NLRP3 inflammasome activation after induction by metabolic danger signals or via protein–protein interactions with NLRP3 that likely occur in metabolic diseases. Understanding these mechanisms will enable the development of specific inhibitors to treat NLRP3-related metabolic diseases.

Free access
Timothy J Dreyer Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK

Search for other papers by Timothy J Dreyer in
Google Scholar
PubMed
Close
,
Jacob AC Keen Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK

Search for other papers by Jacob AC Keen in
Google Scholar
PubMed
Close
,
Leah M Wells Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK

Search for other papers by Leah M Wells in
Google Scholar
PubMed
Close
, and
Scott J Roberts Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK

Search for other papers by Scott J Roberts in
Google Scholar
PubMed
Close

As a key regulator of bone homeostasis, sclerostin has garnered a lot of interest over the last two decades. Although sclerostin is primarily expressed by osteocytes and is well known for its role in bone formation and remodelling, it is also expressed by a number of other cells and potentially plays a role in other organs. Herein, we aim to bring together recent sclerostin research and discuss the effect of sclerostin on bone, cartilage, muscle, liver, kidney and the cardiovascular and immune systems. Particular focus is placed on its role in diseases, such as osteoporosis and myeloma bone disease, and the novel development of sclerostin as a therapeutic target. Anti-sclerostin antibodies have recently been approved for the treatment of osteoporosis. However, a cardiovascular signal was observed, prompting extensive research into the role of sclerostin in vascular and bone tissue crosstalk. The study of sclerostin expression in chronic kidney disease was followed by the investigation of its role in liver–lipid–bone interactions, and the recent discovery of sclerostin as a myokine prompted new research into sclerostin within the bone–muscle relationship. Potentially, the effects of sclerostin reach beyond that of bone alone. We further summarise recent developments in the use of sclerostin as a potential therapeutic for osteoarthritis, osteosarcoma and sclerosteosis. Overall, these new treatments and discoveries illustrate progress within the field, however, also highlight remaining gaps in our knowledge.

Free access
Ken KY Ho Garvan Institute of Medical Research, St. Vincent’s Hospital and the UNSW Sydney, Sydney, New South Wales, Australia

Search for other papers by Ken KY Ho in
Google Scholar
PubMed
Close
,
Anthony J O’Sullivan St. George Hospital and the Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia

Search for other papers by Anthony J O’Sullivan in
Google Scholar
PubMed
Close
, and
Morton G Burt Southern Adelaide Diabetes and Endocrine, Flinders Medical Centre and College of Medicine and Public Health, and Flinders University, Adelaide, South Australia, Australia

Search for other papers by Morton G Burt in
Google Scholar
PubMed
Close

The fact that growth hormone (GH) plays an important role in health after the cessation of growth requiring replacement therapy in adult life has only been recognised in the last three decades. This has only been made possible by recombinant technology providing GH supplies required to undertake investigations in the physiology of GH action and the benefits of replacement therapy in patients identified by rigorously validated diagnostic tests for GH deficiency (GHD). Human studies have revealed important regulatory roles in substrate metabolism, sodium homeostasis, body composition, and physical function. GH-induced anabolism is achieved by stimulating amino acid incorporation into protein while reducing oxidative loss simultaneously enhancing lipid utilisation by stimulating fatty acid oxidation and reducing lipid storage. Sodium and fluid retention are enhanced by activating the renin–angiotensin system and distal renal tubular reabsorption. GH stimulates the aerobic and anaerobic energy systems that underpin muscle and cardiovascular function. These pleiotropic actions explain the clinical picture of increased adiposity, reduced lean mass, and impaired physical and psychological function in the GHD adult, all of which are reversed when GH is replaced. Women require a greater replacement dose of GH than men. This is because androgens enhance while oestrogens attenuate GH action. The oestrogen effect is route-dependent, occurring with oral delivery blunting the liver-mediated actions of GH by directly inhibiting GH receptor signalling, global experience spanning over 30 years has attested to the safety, efficacy, and benefits of replacement therapy for adults with GHD.

Free access
Mari van de Vyver Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Search for other papers by Mari van de Vyver in
Google Scholar
PubMed
Close

Inflammation is part of the body’s innate immune response and is an essential process that not only defends against harmful bacteria and pathogens but also plays a key role in the maintenance and repair of tissues. Under pathological conditions, there is bilateral crosstalk between immune regulation and aberrant metabolism resulting in persistent inflammation in the absence of infection. This phenomenon is referred to as sterile metabolic inflammation (metainflammation) and occurs if the initiating stimulus is not removed or if the resolution process is disrupted. Disruption of this tightly regulated immune response and its failure to resolve as is evident in metabolic disorders is not only associated with disease progression but also leads to immune senescence and should not be neglected in the clinical management of patients. This review gives an overview of the mechanisms underlying chronic metabolic inflammation, the aberrant metabolic activation of innate immune cells (neutrophils, macrophages, mast cells, dendritic cells), and its role in disease progression using obesity–diabetes as a prime example. Addressing the underlying subclinical metabolic inflammation in addition to achieving glucose control may contribute significantly towards therapeutic interventions aimed at preventing the onset of co-morbidities in diabetic patients.

Free access
Samuel M Lee Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA

Search for other papers by Samuel M Lee in
Google Scholar
PubMed
Close
,
Jose Muratalla Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA

Search for other papers by Jose Muratalla in
Google Scholar
PubMed
Close
,
Marta Sierra-Cruz Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA

Search for other papers by Marta Sierra-Cruz in
Google Scholar
PubMed
Close
, and
Jose Cordoba-Chacon Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA

Search for other papers by Jose Cordoba-Chacon in
Google Scholar
PubMed
Close

Peroxisome proliferator-activated receptor γ (PPARγ) belongs to a family of nuclear receptors that could serve as lipid sensors. PPARγ is the target of a group of insulin sensitizers called thiazolidinediones (TZDs) which regulate the expression of genes involved in glucose and lipid metabolism as well as adipokines that regulate metabolic function in other tissues. Non-alcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and is even higher in patients with obesity and insulin resistance. TZD-mediated activation of PPARγ could serve as a good treatment for NAFLD because TZDs have shown anti-fibrogenic and anti-inflammatory effectsin vitro and increase insulin sensitivity in peripheral tissues which improves liver pathology. However, mechanistic studies in mouse models suggest that the activation of PPARγ in hepatocytes might reduce or limit the therapeutic potential of TZD against NAFLD. In this review, we briefly describe the short history of PPAR isoforms, the relevance of their expression in different tissues, as well as the pathogenesis and potential therapeutics for NAFLD. We also discuss some evidence derived from mouse models that could be useful for endocrinologists to assess tissue-specific roles of PPARs, complement reverse endocrinology approaches, and understand the direct role that PPARγ has in hepatocytes and non-parenchymal cells.

Free access
Jasleen Kaur Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Search for other papers by Jasleen Kaur in
Google Scholar
PubMed
Close
and
Elizabeth R Seaquist Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Search for other papers by Elizabeth R Seaquist in
Google Scholar
PubMed
Close

Glucagon is secreted by the pancreatic alpha cell and has long been known to oppose insulin action. A lyophilized form of the hormone has been available to treat episodes of insulin-induced hypoglycemia in insulin-treated people with diabetes for decades, but the difficulty of use was a barrier to widespread utilization. Newer formulations of glucagon are stable at room temperature in single-use devices that many caregivers find are easier to use than the original glucagon emergency kit. In this review , we will review what is known about the role of glucagon in normal physiology and diabetes and then discuss how the research in this area has been translated into treatment for metabolic conditions.

Free access