Browse

You are looking at 101 - 110 of 14,386 items for

  • Refine by access: All content x
Clear All
J Cantley School of Medicine, University of Dundee, Dundee, United Kingdom of Great Britain and Northern Ireland

Search for other papers by J Cantley in
Google Scholar
PubMed
Close
,
D L Eizirik ULB Center for Diabetes Research, Université Libre de Bruxelles Faculté de Médecine, Bruxelles, Belgium

Search for other papers by D L Eizirik in
Google Scholar
PubMed
Close
,
E Latres JDRF International, New York, NY, USA

Search for other papers by E Latres in
Google Scholar
PubMed
Close
,
C M Dayan Cardiff University School of Medicine, Cardiff, United Kingdom of Great Britain and Northern Ireland

Search for other papers by C M Dayan in
Google Scholar
PubMed
Close
, and
the JDRF-DiabetesUK-INNODIA-nPOD Stockholm Symposium 2022
Search for other papers by the JDRF-DiabetesUK-INNODIA-nPOD Stockholm Symposium 2022 in
Google Scholar
PubMed
Close
the JDRF-DiabetesUK-INNODIA-nPOD Stockholm Symposium 2022

There is a growing understanding that the early phases of type 1 diabetes (T1D) are characterised by a deleterious dialogue between the pancreatic beta cells and the immune system. This, combined with the urgent need to better translate this growing knowledge into novel therapies, provided the background for the JDRF–DiabetesUK–INNODIA–nPOD symposium entitled ‘Islet cells in human T1D: from recent advances to novel therapies’, which took place in Stockholm, Sweden, in September 2022. We provide in this article an overview of the main themes addressed in the symposium, pointing to both promising conclusions and key unmet needs that remain to be addressed in order to achieve better approaches to prevent or reverse T1D.

Open access
Sarah L Armour Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Denmark

Search for other papers by Sarah L Armour in
Google Scholar
PubMed
Close
,
Jade E Stanley Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

Search for other papers by Jade E Stanley in
Google Scholar
PubMed
Close
,
James Cantley Division of Cellular and Systems Medicine, School of Medicine, University of Dundee, UK

Search for other papers by James Cantley in
Google Scholar
PubMed
Close
,
E Danielle Dean Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Division of Diabetes, Endocrinology, & Metabolism, Vanderbilt University Medical Center School of Medicine, Nashville, Tennessee, USA

Search for other papers by E Danielle Dean in
Google Scholar
PubMed
Close
, and
Jakob G Knudsen Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Denmark

Search for other papers by Jakob G Knudsen in
Google Scholar
PubMed
Close

Since the discovery of glucagon 100 years ago, the hormone and the pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, alpha cells have been described in the context of glucagon’s role in glucose metabolism in liver, with glucose as the primary nutrient signal regulating alpha cell function. However, current data reveal a more holistic model of metabolic signalling, involving glucagon-regulated metabolism of multiple nutrients by the liver and other tissues, including amino acids and lipids, providing reciprocal feedback to regulate glucagon secretion and even alpha cell mass. Here we describe how various nutrients are sensed, transported and metabolised in alpha cells, providing an integrative model for the metabolic regulation of glucagon secretion and action. Importantly, we discuss where these nutrient-sensing pathways intersect to regulate alpha cell function and highlight key areas for future research.

Free access
Jun Yang Centre of Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Medicine, Monash University, Clayton, Victoria, Australia

Search for other papers by Jun Yang in
Google Scholar
PubMed
Close
,
Morag J Young Cardiovascular Endocrinology Laboratory, Discovery & Preclinical Domain, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

Search for other papers by Morag J Young in
Google Scholar
PubMed
Close
,
Timothy J Cole Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia

Search for other papers by Timothy J Cole in
Google Scholar
PubMed
Close
, and
Peter J Fuller Centre of Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia

Search for other papers by Peter J Fuller in
Google Scholar
PubMed
Close

Primary aldosteronism, or Conn syndrome, is the most common endocrine cause of hypertension. It is associated with a higher risk of cardiovascular, metabolic and renal diseases, as well as a lower quality of life than for hypertension due to other causes. The multi-systemic effects of primary aldosteronism can be attributed to aldosterone-mediated activation of the mineralocorticoid receptor in a range of tissues. In this review, we explore the signalling pathways of the mineralocorticoid receptor, with a shift from the traditional focus on the regulation of renal sodium–potassium exchange to a broader understanding of its role in the modulation of tissue inflammation, fibrosis and remodelling. The appreciation of primary aldosteronism as a multi-system disease with tissue-specific pathophysiology may lead to more vigilant testing and earlier institution of targeted interventions.

Free access
Leonie Cabot Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Straße, Cologne, Germany
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Straße, Cologne, Germany

Search for other papers by Leonie Cabot in
Google Scholar
PubMed
Close
,
Juliet Erlenbeck-Dinkelmann Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Straße, Cologne, Germany

Search for other papers by Juliet Erlenbeck-Dinkelmann in
Google Scholar
PubMed
Close
, and
Henning Fenselau Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Straße, Cologne, Germany
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Straße, Cologne, Germany
Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Straße, Cologne, Germany

Search for other papers by Henning Fenselau in
Google Scholar
PubMed
Close

The brain is tuned to integrate food-derived signals from the gut, allowing it to accurately adjust behavioral and physiological responses in accordance with nutrient availability. A key element of gut-to-brain communication is the relay of neural cues via peripheral sensory neurons (PSN) which harbor functionally specialized peripheral endings innervating the muscular and mucosal layers of gastrointestinal (GI) tract organs. In this review, we detail the properties of GI tract innervating PSN and describe their roles in regulating satiation and glucose metabolism in response to food consumption. We discuss the complex anatomical organization of vagal and spinal PSN subtypes, their peripheral and central projection patterns, and describe the limitations of unselective lesion and ablation approaches to investigate them. We then highlight the recent identification of molecular markers that allow selective targeting of PSN subtypes that innervate GI tract organs. This has facilitated accurately determining their projections, monitoring their responses to gut stimuli, and manipulating their activity. We contend that these recent developments have significantly improved our understanding of PSN-mediated gut-to-brain communication, which may open new therapeutic windows for the treatment of metabolic disorders, such as obesity and type 2 diabetes.

Free access
Romy I Kerbus Department of Anatomy and Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand

Search for other papers by Romy I Kerbus in
Google Scholar
PubMed
Close
,
Megan A Inglis Department of Anatomy and Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand

Search for other papers by Megan A Inglis in
Google Scholar
PubMed
Close
, and
Greg M Anderson Department of Anatomy and Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand

Search for other papers by Greg M Anderson in
Google Scholar
PubMed
Close

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Approximately half of the diagnosed individuals also experience the metabolic syndrome. Central and peripheral resistance to the hormones insulin and leptin have been reported to contribute to both metabolic and reproductive dysregulation. In PCOS and preclinical PCOS animal models, circulating insulin and leptin levels are often increased in parallel with the development of hormone resistance; however, it remains uncertain whether these changes contribute to the PCOS state. In this study, we tested whether central actions of protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3), negative regulators of insulin and leptin signaling pathways, respectively, play a role in the development of PCOS-like phenotype. A peripubertal dihydrotestosterone (DHT) excess PCOS-like mouse model was used, which exhibits both metabolic and reproductive dysfunction. Mice with knockout of the genes encoding PTP1B and SOCS3 from forebrain neurons were generated, and metabolic and reproductive functions were compared between knockout and control groups. DHT treatment induced mild insulin resistance but not leptin resistance, so the role of SOCS3 could not be tested. As expected, DHT excess abolished estrous cycles and corpora lutea presence and caused increased visceral adiposity and fasting glucose levels. Knockout mice did not show any rescue of reproductive dysfunction but did have reduced adiposity compared to the control DHT mice. These data suggest that negative regulation of central insulin signaling by PTP1B is not responsible for peripubertal DHT excess-induced reproductive impairments but may mediate its increased adiposity effects.

Restricted access
Lingyun Lu Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

Search for other papers by Lingyun Lu in
Google Scholar
PubMed
Close
and
Li Tian Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

Search for other papers by Li Tian in
Google Scholar
PubMed
Close

Estrogens (estradiol, estriol, and estrone) are important hormones that directly and indirectly regulate the metabolism and function of bone and skeletal muscle via estrogen receptors. Menopause causes a dramatic reduction in the concentration of estrogen in the body. This contributes to a decline in bone and skeletal muscle function, thereby resulting in osteoporosis and sarcopenia. Menopausal women often experience osteoporosis and muscle wasting, and clinicians recognize estrogen as playing an important role in these conditions, particularly in women. Bone and muscle are closely related endocrine tissues that synthesize and produce various cytokines. These bone- and muscle-derived cytokines, including interleukin-6, irisin, β-aminoisobutyric acid, osteocalcin, fibroblast growth factor-23, and sclerostin, regulate both local and distant tissues, and they mediate the crosstalk between bone and skeletal muscle. This review examines the metabolic effects of estrogen on bone and skeletal muscle and describes cytokine-mediated bone–muscle crosstalk in conditions of estrogen deficiency.

Free access
Daniella Bianchi Reis Insuela Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Daniella Bianchi Reis Insuela in
Google Scholar
PubMed
Close
,
Maximiliano Ruben Ferrero Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Maximiliano Ruben Ferrero in
Google Scholar
PubMed
Close
,
Amanda da Silva Chaves Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Amanda da Silva Chaves in
Google Scholar
PubMed
Close
,
Diego de Sá Coutinho Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Diego de Sá Coutinho in
Google Scholar
PubMed
Close
,
Nathalia dos Santos Magalhães Laboratório de Pesquisa em Infecção Hospitalar, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Nathalia dos Santos Magalhães in
Google Scholar
PubMed
Close
,
Ana Carolina Santos de Arantes Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Ana Carolina Santos de Arantes in
Google Scholar
PubMed
Close
,
Adriana Ribeiro Silva Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil
Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação (INCT-NIM), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Adriana Ribeiro Silva in
Google Scholar
PubMed
Close
,
Patrícia Machado Rodrigues e Silva Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Patrícia Machado Rodrigues e Silva in
Google Scholar
PubMed
Close
,
Marco Aurélio Martins Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Marco Aurélio Martins in
Google Scholar
PubMed
Close
, and
Vinicius Frias Carvalho Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil
Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação (INCT-NIM), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil

Search for other papers by Vinicius Frias Carvalho in
Google Scholar
PubMed
Close

Prior research demonstrated that glucagon has protective roles against inflammation, but its effect on the resolution of inflammation remains elusive. Using in vitro and in vivo approaches, this study aimed to investigate the pro-resolving potential of glucagon on pulmonary neutrophilic inflammation caused by lipopolysaccharide. Lipopolysaccharide induced an increase in the proportions of neutrophils positives to glucagon receptor (GcgR) in vitro. In addition, lipopolysaccharide induced an increase in the neutrophil accumulation and expression of GcgR by the inflammatory cells in the lungs, however, without altering glucagon levels. Intranasal treatment with glucagon, at the peak of neutrophilic inflammation, reduced the neutrophil number in the bronchoalveolar lavage (BAL), and lung tissue within 24 h. The reduction of neutrophilic inflammation provoked by glucagon was accompanied by neutrophilia in the blood, an increase in the apoptosis rate of neutrophils in the BAL, enhance in the pro-apoptotic Bax protein expression, and decrease in the anti-apoptotic Bcl-2 protein levels in the lung. Glucagon also induced a rise in the cleavage of caspase-3 in the lungs; however, it was not significant. Glucagon inhibited the levels of IL-1β and TNF-α while increasing the content of pro-resolving mediators transforming growth factor (TGF-β1) and PGE2 in the BAL and lung. Finally, glucagon inhibited lipopolysaccharide-induced airway hyper-reactivity, as evidenced by the reduction in lung elastance values in response to methacholine. In conclusion, glucagon-induced resolution of neutrophilic inflammation by promoting cessation of neutrophil migration and a rise of neutrophil apoptosis and the levels of pro-resolving mediators TGF-β1 and PGE2.

Restricted access
Kevin H Tsai ANZAC Research Institute, Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia

Search for other papers by Kevin H Tsai in
Google Scholar
PubMed
Close
and
Mark S Cooper ANZAC Research Institute, Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia

Search for other papers by Mark S Cooper in
Google Scholar
PubMed
Close

Endogenous glucocorticoids and commonly used oral glucocorticoids have the property of existing in an inactive and active form in vivo. The inactive form can be converted back to the active form, or ‘recycled’ in cells and tissues that express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. This recycling provides an important contribution to the action of glucocorticoids. This review examines the literature relating to the importance of 11β-HSD1 activity during glucocorticoid treatment, with an emphasis on studies examining bone and joint disease and the ability of glucocorticoids to suppress inflammatory damage in models of arthritis. Animal models with global or selective deletion of 11β-HSD1 have determined the extent to which this recycling is important in normal physiology and during treatment with oral glucocorticoids. These studies demonstrate that 11β-HSD1-mediated recycling of inactive glucocorticoids has a substantial action and indeed is responsible for the majority of the effects of orally administered glucocorticoids on a range of tissues. Importantly, the anti-inflammatory actions of glucocorticoids appear largely through this mechanism such that mice that lack 11β-HSD1 are resistant to the anti-inflammatory actions of glucocorticoids. The recognition that to a large extent the circulating inactive counterpart of these glucocorticoids is more important to anti-inflammatory effects than the active glucocorticoid presents novel opportunities to more selectively target glucocorticoids to tissues or to reduce the likely side effects.

Free access
Caitlin S Wyrwoll School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia
Telethon Kids Institute, Perth, Australia
Healthy Environments and Lives (HEAL) Network

Search for other papers by Caitlin S Wyrwoll in
Google Scholar
PubMed
Close

The incidence and severity of heatwaves are increasing globally with concomitant health complications. Pregnancy is a critical time in the life course at risk of adverse health outcomes due to heat exposure. Dynamic physiological adaptations, which include altered thermoregulatory pathways, occur in pregnancy. If heat dissipation is ineffective, maternal and neonate health outcomes can be compromised. Indeed, epidemiological studies and animal models reveal that exposure to heat in pregnancy likely elicits an array of health complications including miscarriage, congenital anomalies, low birth weight, stillbirth, and preterm birth. Despite these associations, the reasons for why these complications occur are unclear. An array of physiological and endocrine changes in response to heat exposure in pregnancy likely underpin the adverse health outcomes, but currently, conclusive evidence is sparse. Accompanying these fundamental gaps in knowledge is a poor understanding of what exact climatic conditions challenge pregnant physiology. Moreover, the overlay of thermoregulatory-associated behaviours such as physical activity needs to be taken into consideration when assessing the risks to human health and identifying critical populations at risk. While the health impacts from heat are largely preventable through strategic interventions, for the related clinical practice, public health, and policy approaches to be effective, the gaps in basic science understanding urgently need to be addressed.

Free access
Alejandra Abeledo-Machado Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by Alejandra Abeledo-Machado in
Google Scholar
PubMed
Close
,
Dana Bornancini Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by Dana Bornancini in
Google Scholar
PubMed
Close
,
Milagros Peña-Zanoni Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by Milagros Peña-Zanoni in
Google Scholar
PubMed
Close
,
María Andrea Camilletti Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by María Andrea Camilletti in
Google Scholar
PubMed
Close
,
Erika Yanil Faraoni Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by Erika Yanil Faraoni in
Google Scholar
PubMed
Close
, and
Graciela Díaz-Torga Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Search for other papers by Graciela Díaz-Torga in
Google Scholar
PubMed
Close

Serum prolactin increases from birth to adulthood in rats, being higher in females from birth. The maturation of hypothalamic/gonadal prolactin-releasing and -inhibiting factors does not explain some sex differences observed. During the first weeks of life, prolactin secretion increases, even when lactotrophs are isolated in vitro, in the absence of those controls, suggesting the participation of intra-pituitary factors in this control. The present work aimed to study the involvement of pituitary activins in the regulation of prolactin secretion during post-natal development. Sex differences were also highlighted. Female and male Sprague–Dawley rats at 11, 23 and 45postnatal days were used. Pituitary expression of activin subunits and activin receptors was maximum in p11 female pituitaries, being even higher than that observed in males. Those expressions decrease with age in females, and then the gender differences disappear at p23. Inhbb expression strongly increases at p45 in males, being the predominant subunit in this sex in adulthood. Activin inhibition of prolactin is mediated by the inhibition of Pit-1 expression. This action involves not only the canonical pSMAD pathway but also the phosphorylation of p38MAPK. At p11, almost all lactotrophs express p-p38MAPK in females, and its expression decreases with age with a concomitant increase in Pit-1. Our findings suggest that the inhibitory regulation of pituitary activins on prolactin secretion is sex specific; this regulation is more relevant in females during the first week of life and decreases with age; this intra-pituitary regulation is involved in the sex differences observed in serum prolactin levels during postnatal development.

Restricted access