scholarly journals Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism

2021 ◽  
Vol 9 ◽  
Author(s):  
Julian D. Gross ◽  
Catherine J. Pears
Keyword(s):  
Cell Fate ◽  
Relative Strength ◽  
Human Diseases ◽  
Therapeutic Interventions ◽  
Energy Status ◽  
Highly Active ◽  
The Social ◽  
Ampk Activity ◽  
Acidic Compartments

mTORC1 and AMPK are mutually antagonistic sensors of nutrient and energy status that have been implicated in many human diseases including cancer, Alzheimer’s disease, obesity and type 2 diabetes. Starved cells of the social amoeba Dictyostelium discoideum aggregate and eventually form fruiting bodies consisting of stalk cells and spores. We focus on how this bifurcation of cell fate is achieved. During growth mTORC1 is highly active and AMPK relatively inactive. Upon starvation, AMPK is activated and mTORC1 inhibited; cell division is arrested and autophagy induced. After aggregation, a minority of the cells (prestalk cells) continue to express much the same set of developmental genes as during aggregation, but the majority (prespore cells) switch to the prespore program. We describe evidence suggesting that overexpressing AMPK increases the proportion of prestalk cells, as does inhibiting mTORC1. Furthermore, stimulating the acidification of intracellular acidic compartments likewise increases the proportion of prestalk cells, while inhibiting acidification favors the spore pathway. We conclude that the choice between the prestalk and the prespore pathways of cell differentiation may depend on the relative strength of the activities of AMPK and mTORC1, and that these may be controlled by the acidity of intracellular acidic compartments/lysosomes (pHv), cells with low pHv compartments having high AMPK activity/low mTORC1 activity, and those with high pHv compartments having high mTORC1/low AMPK activity. Increased insight into the regulation and downstream consequences of this switch should increase our understanding of its potential role in human diseases, and indicate possible therapeutic interventions.

Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?

2021 ◽  
pp. 107424842110069
Author(s):  
Emir M. Muzurović ◽  
Snežana Vujošević ◽  
Dimitri P. Mikhailidis
Keyword(s):  
Myocardial Dysfunction ◽  
Biologically Active ◽  
Therapeutic Interventions ◽  
Cvd Risk ◽  
Fat Deposits ◽  
Patients With Diabetes ◽  
Calorie Diet ◽  
Cv Disease ◽  
Secretory Pattern

Diabetes mellitus (DM) is a chronic and complex metabolic disorder and also an important cause of cardiovascular (CV) disease (CVD). Patients with type 2 DM (T2DM) and obesity show a greater propensity for visceral fat deposition (and excessive fat deposits elsewhere) and the link between adiposity and CVD risk is greater for visceral than for subcutaneous (SC) adipose tissue (AT). There is growing evidence that epicardial AT (EAT) and pericardial AT (PAT) play a role in the development of DM-related atherosclerosis, atrial fibrillation (AF), myocardial dysfunction, and heart failure (HF). In this review, we will highlight the importance of PAT and EAT in patients with DM. We also consider therapeutic interventions that could have a beneficial effect in terms of reducing the amount of AT and thus CV risk. EAT is biologically active and a likely determinant of CV morbidity and mortality in patients with DM, given its anatomical characteristics and proinflammatory secretory pattern. Consequently, modification of EAT/PAT may become a therapeutic target to reduce the CV burden. In patients with DM, a low calorie diet, exercise, antidiabetics and statins may change the quantity of EAT, PAT or both, alter the secretory pattern of EAT, improve the metabolic profile, and reduce inflammation. However, well-designed studies are needed to clearly define CV benefits and a therapeutic approach to EAT/PAT in patients with DM.

scholarly journals Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xudong Zhu ◽  
Zhiyang Chen ◽  
Weiyan Shen ◽  
Gang Huang ◽  
John M. Sedivy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
State Of The Art ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Cell Fate Decision ◽  
The Past ◽  
Fate Decision ◽  
The Individual ◽  
Remarkable Progress

AbstractRemarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

scholarly journals Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

2007 ◽  
Vol 192 (3) ◽  
pp. 605-614 ◽  
Author(s):  
Fang Cai ◽  
Armen V Gyulkhandanyan ◽  
Michael B Wheeler ◽  
Denise D Belsham
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Cell Model ◽  
Neuronal Cell ◽  
Cell Types ◽  
Glucose Sensing ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

Physical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults

2018 ◽  
Vol 54 (4) ◽  
pp. 238-244 ◽  
Author(s):  
David Martinez-Gomez ◽  
Irene Esteban-Cornejo ◽  
Esther Lopez-Garcia ◽  
Esther García-Esquinas ◽  
Kabir P Sadarangani ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Highly Active ◽  
Atherogenic Dyslipidaemia

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

Enabling Occupation: The Importance of an Affirming Environment

2001 ◽  
Vol 68 (2) ◽  
pp. 80-89 ◽  
Author(s):  
Karen L. Rebeiro
Keyword(s):  
Mental Illness ◽  
Qualitative Study ◽  
Social Environment ◽  
Occupational Therapists ◽  
Therapeutic Interventions ◽  
Occupational Engagement ◽  
Occupational Performance ◽  
The Social ◽  
The Individual ◽  
Over Time

Occupational therapists have become increasingly concerned with factors beyond the individual which impact occupational performance. Several recent models propose that the environment is a significant influence on occupational performance and upon its meaningfulness. An in-depth, qualitative study was conducted which explored the meaning of occupational engagement for eight women with mental illness (Rebeiro & Cook, 1999). This study yielded several important insights about the environment, which have recently been replicated by Legault and Rebeiro (2001) and Rebeiro, Day, Semeniuk, O'Brien, and Wilson (In Press). Participants suggested that environments that provide opportunity, and not prescription are more conducive to fostering occupational performance. Participants further suggested that an environment that provides Affirmation of the individual as a person of worth, a place to belong, and a place to be supported, enables occupational performance over time. A series of research studies indicated that the social environment is an important consideration in planning therapeutic interventions which aim to enable occupation. Implications for occupational therapy practice, education and research are offered

SPREADING ACTIVATION OVER ONTOLOGY-BASED RESOURCES: FROM PERSONAL CONTEXT TO WEB SCALE REASONING

2010 ◽  
Vol 04 (01) ◽  
pp. 59-102 ◽  
Author(s):  
ALAN DIX ◽  
AKRIVI KATIFORI ◽  
GIORGOS LEPOURAS ◽  
COSTAS VASSILAKIS ◽  
NADEEM SHABIR
Keyword(s):  
User Interaction ◽  
Knowledge Bases ◽  
Spreading Activation ◽  
Personal Ontology ◽  
Highly Active ◽  
The Social ◽  
Web Of Data ◽  
Working Set ◽  
Personal Context ◽  
Model Context

This paper describes methods to allow spreading activation to be used on web-scale information resources. Existing work has shown that spreading activation can be used to model context over small personal ontologies, which can be used to assist in various user activities, for example, in auto-completing web forms. This previous work is extended and methods are developed by which large external repositories, including corporate information and the web, can be linked to the user's personal ontology and thus allow automated assistance that is able to draw on the entire web of data. The basic idea is to augment the personal ontology with cached data from external repositories, where the choice of data to fetch or discard is related to the level of activation of entities already in the personal ontology or cached data. This relies on the assumption that the working set of highly active entities is relatively small; empirical results are presented, which suggest these assumptions are likely to hold. Implications of the techniques are discussed for user interaction and for the social web. In addition, warm world reasoning is proposed, applying rule-based reasoning over activated entities, potentially merging symbolic and sub-symbolic reasoning over web-scale knowledge bases.

scholarly journals Education for type 2 diabetes mellitus self-care: from compliance to empowerment

2009 ◽  
Vol 13 (30) ◽  
pp. 93-106 ◽  
Author(s):  
Antonio Pithon Cyrino ◽  
Lilia Blima Schraiber ◽  
Ricardo Rodrigues Teixeira
Keyword(s):  
Social Sciences ◽  
Chronic Conditions ◽  
Self Care ◽  
Self Management ◽  
Degenerative Diseases ◽  
Cognitive Autonomy ◽  
The Social ◽  
Transmission Of Information ◽  
Traditional Approaches

Through a critical review of the literature on education for diabetes self-care and self-management, it was sought to point out the inappropriateness of traditional approaches towards compliance with treatment and transmission of information, considering the complexity of self-care under chronic conditions. The influence of the social sciences on the field of studies on chronic degenerative diseases in general, and diabetes in particular, was explored. From this perspective, it can be recognized that the fields of anthropology and sociology have been incorporated into research focusing more on individuals as patients, and on the experience gained through this process. Recently, there has been a slight change within the field of health education research relating to diabetes, with the introduction of strategies that seek to value the experience and autonomy of patients as self-care agents. This paper discusses the strategy for empowerment in education for diabetes self-care and self-management, as a dialogue-focused practice that respects patients' moral and cognitive autonomy.

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