scholarly journals Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 108
Author(s):  
Philip Newsholme ◽  
Jordan Rowlands ◽  
Roselyn Rose’Meyer ◽  
Vinicius Cruzat
Keyword(s):  
Chronic Exposure ◽  
Cell Damage ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Therapeutic Drug ◽  
Inflammatory Factor ◽  
Β Cell ◽  
Regulatory Processes ◽  
Drug Concentrations ◽  
And Function

Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.

scholarly journals Metabolic reprogramming in macrophage responses

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yang Liu ◽  
Ruyi Xu ◽  
Huiyao Gu ◽  
Enfan Zhang ◽  
Jianwei Qu ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Macrophage Phenotype ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Therapeutic Implications ◽  
Metabolic Characteristics ◽  
Main Component ◽  
And Function ◽  
Inflammatory Macrophages

AbstractMacrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function. Generally, pro-inflammatory macrophages (M1) rely mainly on glycolysis and exhibit impairment of the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS), whereas anti-inflammatory macrophages (M2) are more dependent on mitochondrial OXPHOS. However, accumulating evidence suggests that macrophage metabolism is not as simple as previously thought. This review discusses recent advances in immunometabolism and describes how metabolism determines macrophage phenotype and function. In addition, we describe the metabolic characteristics of TAMs as well as their therapeutic implications. Finally, we discuss recent obstacles facing this area as well as promising directions for future study.

Tead1 Reciprocally Regulates Adult β-Cell Proliferation and Function to Maintain Glucose Homeostasis

2020 ◽  
Author(s):  
Jeongkyung Lee ◽  
Ruya Liu ◽  
Byung S. Kim ◽  
Yiqun Zhang ◽  
Feng Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Β Cell ◽  
And Function

Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Francine Rubião ◽  
Alan Cezar Faria Araújo ◽  
João Bernardo Sancio ◽  
Bárbara Silva Nogueira ◽  
Juçara Ribeiro Franca ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
T Test ◽  
Controlled Study ◽  
Therapeutic Drug ◽  
Eye Drops ◽  
Open Angle ◽  
Drug Concentrations

Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

scholarly journals Repair cell first, then regenerate the tissues and organs

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao-Bing Fu
Keyword(s):  
Tissue Repair ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Severe Trauma ◽  
Basic Unit ◽  
Basic Process ◽  
Tissue Repair And Regeneration ◽  
Healing Tissue ◽  
Organ Repair ◽  
And Function

AbstractWound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly; however, the basic process of repair at the cell level is often neglected. Because the cell is the basic unit of organism structure and function; cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury. Then, damage to tissues and organs occurs with massive cell damage, apoptosis and even cell death. Thus, how to achieve the aim of perfect repair and regeneration? The basic process of tissue or organ repair and regeneration should involve repair of cells first, then tissues and organs. In this manuscript, it is my consideration about how to repair the cell first, then regenerate the tissues and organs.

scholarly journals Transcriptome and metabolome analyses of cold and darkness-induced pellicle cysts of Scrippsiella trochoidea

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin Guo ◽  
Zhaohui Wang ◽  
Lei Liu ◽  
Yang Li
Keyword(s):  
Signal Transduction ◽  
Sexual Reproduction ◽  
Harmful Algal Bloom ◽  
Transcriptional Response ◽  
Tca Cycle ◽  
Adaptive Strategy ◽  
Cyst Formation ◽  
Metabolite Profile ◽  
Scrippsiella Trochoidea ◽  
Regulatory Processes

Abstract Background Dinoflagellates are a group of unicellular organisms that are a major component of aquatic eukaryotes and important contributors to marine primary production. Nevertheless, many dinoflagellates are considered harmful algal bloom (HAB) species due to their detrimental environmental and human health impacts. Cyst formation is widely perceived as an adaptive strategy of cyst-forming dinoflagellates in response to adverse environmental conditions. Dinoflagellate cysts play critical roles in bloom dynamics. However, our insight into the underlying molecular basis of encystment is still limited. To investigate the molecular processes regulating encystment in dinoflagellates, transcriptome and metabolome investigations were performed on cold and darkness-induced pellicle cysts of Scrippsiella trochoidea. Results No significant transcriptional response was observed at 2 h; however, massive transcriptome and metabolome reprogramming occurred at 5 h and in pellicle cysts. The gene-to-metabolite network demonstrated that the initial transformation from vegetative cells into pellicle cysts was highly energy demanding through the activation of catabolism, including glycolysis, β-oxidation, TCA cycle and oxidative phosphorylation, to cope with cold-darkness-induced stress. However, after transformation into pellicle cysts, the metabolism was greatly reduced, and various sugars, polyunsaturated fatty acids and amino acids accumulated to prolong survival. The identification of 56 differentially expressed genes (DEGs) related to signal transduction indicated that S. trochoidea received a cold-darkness signal that activated multiple signal transduction pathways, leading to encystment. The elevated expression of genes encoding enzymes involved in ROS stress suggested that pellicle cysts respond to increased oxidative stress. Several cell cycle-related genes were repressed. Intriguingly, 11 DEGs associated with sexual reproduction suggested that pellicle cysts (or some portion thereof) may be a product of sexual reproduction. Conclusions This study provides the first transcriptome and metabolome analyses conducted during the encystment of S. trochoidea, an event that requires complex regulatory mechanisms and impacts on population dynamics. The results reveal comprehensive molecular regulatory processes underlying life cycle regulation in dinoflagellates involving signal transduction, gene expression and metabolite profile, which will improve our ability to understand and monitor dinoflagellate blooms.

scholarly journals Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 903
Author(s):  
Xiao-Mei Zhang ◽  
De-Gao Chen ◽  
Shengwen Calvin Li ◽  
Bo Zhu ◽  
Zhong-Jun Li
Keyword(s):  
Metabolic Regulation ◽  
Transcriptional Profiling ◽  
Tumor Development ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Functional Heterogeneity ◽  
Tumor Associated Macrophages ◽  
Metabolic Remodeling ◽  
And Function ◽  
Mapping Models

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous “camouflage” in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages’ ontogeny in macrophages’ functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs’ origins may help understand the classification of TAMs’ population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies.

scholarly journals Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 384
Author(s):  
Shufeng Wang ◽  
Xin Yang ◽  
Feng Liu ◽  
Xinzheng Wang ◽  
Xuemin Zhang ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Drug Targets ◽  
High Sensitivity ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
Metabolic Reprogramming ◽  
Pyrimidine Metabolism ◽  
Rapid Separation ◽  
Hexosamine Pathway ◽  
Hep3b Cells

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.

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