scholarly journals Impact of Incretin-Based Therapies on Adipokines and Adiponectin

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Habib Yaribeygi ◽  
Mina Maleki ◽  
Stephen L. Atkin ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Antidiabetic Drugs ◽  
Hormonal Effects ◽  
Cellular Processes ◽  
Carbohydrate Homeostasis ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Adipokines are a family of hormones and cytokines with both pro- and anti-inflammatory effects released into the circulation to exert their hormonal effects. Adipokines are closely involved in most metabolic pathways and play an important modulatory role in lipid and carbohydrate homeostasis as they are involved in the pathophysiology of most metabolic disorders. Incretin-based therapy is a newly introduced class of antidiabetic drugs that restores euglycemia through several cellular processes; however, its effect on adipokines expression/secretion is not fully understood. In this review, we propose that incretin-based therapy may function through adipokine modulation that may result in pharmacologic properties beyond their direct antidiabetic effects, resulting in better management of diabetes and diabetes-related complications.

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

scholarly journals OP0277-PARE METABERN, THE EUROPEAN REFERENCE NETWORK FOR RARE HEREDITARY DISEASES: STRUCTURE, OBJECTIVES, METABOLIC RMDS AND THE ROLES OF EUROPEAN PATIENT ADVOCACY GROUPS (EPAGS)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 168.2-168
Author(s):  
L. Wagner ◽  
S. Sestini ◽  
C. Brown ◽  
A. Finglas ◽  
R. Francisco ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Social Science ◽  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Clinical Care ◽  
Single Point ◽  
Link Type ◽  
The Impact

Background:Inborn metabolic disorders (IMDs) currently encompass more than 1,500 diseases with new ones still to be identified1. Each of them is characterised by a genetic defect affecting a metabolic pathway. Only few of them have curative treatments, that target the respective metabolic pathway. Commonly, treatment examples include diet, substrate reduction therapies, enzyme replacement therapies, gene therapy and biologicals, enabling IMD-patient now to survive to adulthood. About 30 % of all IMDs involve the musculoskeletal system and are here referred to as rare metabolic RMDs. Generally, IMDs are very heterogenous with respect to symptoms and severity, often being systemic and affecting more children than adults. Thus, challenges include certified advanced training of adult metabolic experts, standardised transition plans, social support and development of therapies for diseases that do not have any cure yet.Objectives:Introduction of MetabERN, its structure and objectives, highlighting on the unique features and challenges of metabolic RMDs and describing the involvement of patient representation in MetabERN.Methods:MetabERN is stratified in 7 subnetworks (SNW) according to the respective metabolic pathways and 9 work packages (WP), including administration, dissemination, guidelines, virtual counselling framework, research/clinical trials, continuity of care, education and patient involvement. The patient board involves a steering committee and single point of contacts for each subnetwork and work package, respectively2. Projects include identifying the need of implementing social science to assess the psycho-socio-economic burden of IMDs, webinars on IMDs and their transition as well as surveys on the impact of COVID-193 on IMD-patients and health care providers (HCPs), social assistance for IMD-patients and analysing the transition landscape within Europe.Results:The MetabERN structure enables bundling of expertise, capacity building and knowledge transfer for faster diagnosis and better health care. Rare metabolic RMDs are present in all SNWs that require unique treatments according to their metabolic pathways. Implementation of social science to assess the psycho-socio-economic burden of IMDs is still underused. Involvement of patient representatives is essential for a holistic healthcare not only focusing on clinical care, but also on the quality of life for IMD-patients. Surveys identified unmet needs of patient care, patients having little information on national support systems and structural deficits of healthcare systems to ensure HCP can provide adequate clinical care during transition phases. These results are collected by MetabERN and forwarded to the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC) to be addressed further.Conclusion:MetabERN offers an infrastructure of virtual healthcare for patients with IMDs. Thus, in collaboration with ERN ReCONNET, MetabERN can assist in identifying rare metabolic disorders of RMDs to shorten the odyssey of diagnosis and advise on their respective therapies. On the other hand, MetabERN can benefit from EULAR’s longstanding experience regarding issues affecting the quality of life, all RMD patients are facing, such as pain, stiffness, fatigue, rehabilitation, maintaining work and disability claims.References:[1]IEMbase - Inborn Errors of Metabolism Knowledgebase http://www.iembase.org/ (accessed Jan 29, 2021).[2]MetabERN: European Refence Network for Hereditary Metabolic Disorders https://metab.ern-net.eu/ (accessed Jan 29, 2021).[3]Lampe, C.; Dionisi-Vici, C.; Bellettato, C. M.; Paneghetti, L.; van Lingen, C.; Bond, S.; Brown, C.; Finglas, A.; Francisco, R.; Sestini, S.; Heard, J. M.; Scarpa, M.; MetabERN collaboration group. The Impact of COVID-19 on Rare Metabolic Patients and Healthcare Providers: Results from Two MetabERN Surveys. Orphanet J. Rare Dis.2020, 15 (1), 341. https://doi.org/10.1186/s13023-020-01619-x.Acknowledgements:The authors thank the MetabERN collaboration group, the single point of contacts (SPOC) of the MetabERN patient board and the Transition Project Working Group (TPWG)Disclosure of Interests:None declared

scholarly journals Effects of microcompartmentation on flux distribution and metabolic pools in Chlamydomonas reinhardtii chloroplasts

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anika Küken ◽  
Frederik Sommer ◽  
Liliya Yaneva-Roder ◽  
Luke CM Mackinder ◽  
Melanie Höhne ◽  
...  
Keyword(s):  
Experimental Data ◽  
Chlamydomonas Reinhardtii ◽  
Metabolic Pathways ◽  
Metabolic Flux ◽  
Flux Distribution ◽  
Photosynthetic Performance ◽  
Computational Approach ◽  
Cellular Processes ◽  
Diffusional Barrier ◽  
Computational Strategy

Cells and organelles are not homogeneous but include microcompartments that alter the spatiotemporal characteristics of cellular processes. The effects of microcompartmentation on metabolic pathways are however difficult to study experimentally. The pyrenoid is a microcompartment that is essential for a carbon concentrating mechanism (CCM) that improves the photosynthetic performance of eukaryotic algae. Using Chlamydomonas reinhardtii, we obtained experimental data on photosynthesis, metabolites, and proteins in CCM-induced and CCM-suppressed cells. We then employed a computational strategy to estimate how fluxes through the Calvin-Benson cycle are compartmented between the pyrenoid and the stroma. Our model predicts that ribulose-1,5-bisphosphate (RuBP), the substrate of Rubisco, and 3-phosphoglycerate (3PGA), its product, diffuse in and out of the pyrenoid, respectively, with higher fluxes in CCM-induced cells. It also indicates that there is no major diffusional barrier to metabolic flux between the pyrenoid and stroma. Our computational approach represents a stepping stone to understanding microcompartmentalized CCM in other organisms.

scholarly journals Pathway swapping: Toward modular engineering of essential cellular processes

2016 ◽  
Vol 113 (52) ◽  
pp. 15060-15065 ◽  
Author(s):  
Niels G. A. Kuijpers ◽  
Daniel Solis-Escalante ◽  
Marijke A. H. Luttik ◽  
Markus M. M. Bisschops ◽  
Francine J. Boonekamp ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Metabolic Pathways ◽  
Applied Research ◽  
Central Metabolism ◽  
Microbial Genomes ◽  
Cellular Processes ◽  
Recent Developments ◽  
One Step ◽  
Saccharomyces Kudriavzevii

Recent developments in synthetic biology enable one-step implementation of entire metabolic pathways in industrial microorganisms. A similarly radical remodelling of central metabolism could greatly accelerate fundamental and applied research, but is impeded by the mosaic organization of microbial genomes. To eliminate this limitation, we propose and explore the concept of “pathway swapping,” using yeast glycolysis as the experimental model. Construction of a “single-locus glycolysis” Saccharomyces cerevisiae platform enabled quick and easy replacement of this yeast’s entire complement of 26 glycolytic isoenzymes by any alternative, functional glycolytic pathway configuration. The potential of this approach was demonstrated by the construction and characterization of S. cerevisiae strains whose growth depended on two nonnative glycolytic pathways: a complete glycolysis from the related yeast Saccharomyces kudriavzevii and a mosaic glycolysis consisting of yeast and human enzymes. This work demonstrates the feasibility and potential of modular, combinatorial approaches to engineering and analysis of core cellular processes.

scholarly journals Salvianolic Acid A Ameliorates Early-Stage Atherosclerosis Development by Inhibiting NLRP3 Inflammasome Activation in Zucker Diabetic Fatty Rats

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1089 ◽  
Author(s):  
Quanxin Ma ◽  
Qinqin Yang ◽  
Jiaojiao Chen ◽  
Chen Yu ◽  
Lizong Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Salvia Miltiorrhiza ◽  
Blood Cholesterol ◽  
Inflammasome Activation ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
Anti Inflammatory

Salvianolic acid A (SAA), an important bioactive polyphenolic acid found in Salvia miltiorrhiza Bunge, may be used for treating metabolic disorders due to its anti-inflammatory activity. Since chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS), SAA may have beneficial effects on AS. Here, we evaluated the effects of SAA on metabolic disorders in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet and Vitamin D3 injections. Compared with the model group, the SAA high dosage (1 mg/kg) group exhibited decreased hemoglobin A1C levels but unchanged blood glucose levels. The disrupted lipid profiles were ameliorated by SAA, with significantly decreased levels of blood cholesterol, LDL-C and triglyceride. The protective effects of SAA against early AS were further confirmed by histopathological examination of aortic tissues. In addition, we observed that SAA decreased serum hs-CRP levels and suppressed the activation of NLRP3 inflammasome and NF-κB signaling in aortic tissues of ZDF rats. Collectively, our results demonstrate the potential of SAA to alleviate AS and T2DM in ZDF rats as a result of its anti-inflammatory effects.

scholarly journals Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1219 ◽  
Author(s):  
Hyung Muk Choi ◽  
Hari Madhuri Doss ◽  
Kyoung Soo Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Metabolic Disorders ◽  
Serum Levels ◽  
High Serum ◽  
Low Molecular Weight ◽  
High Serum Level ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.

scholarly journals Neuroprotective Mechanisms of PPARδ: Modulation of Oxidative Stress and Inflammatory Processes

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Caroline I. Schnegg ◽  
Mike E. Robbins
Keyword(s):  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Cellular Processes ◽  
Wide Range ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Chronic Injuries ◽  
Neuroprotective Efficacy ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARα,δ, andγ) are ligand-activated transcription factors that regulate a wide range of cellular processes, including inflammation, proliferation, differentiation, metabolism, and energy homeostasis. All three PPAR subtypes have been identified in the central nervous system (CNS) of rodents. While PPARαand PPARγare expressed in more restricted areas of the CNS, PPARδis ubiquitously expressed and is the predominant subtype. Although data regarding PPARδare limited, studies have demonstrated that administration of PPARδagonists confers neuroprotection following various acute and chronic injuries to the CNS, such as stroke, multiple sclerosis, and Alzheimer's disease. The antioxidant and anti-inflammatory properties of PPARδagonists are thought to underly their neuroprotective efficacy. This review will focus on the putative neuroprotective benefits of therapeutically targeting PPARδin the CNS, and specifically, highlight the antioxidant and anti-inflammatory functions of PPARδagonists.

Le acidure organiche

1996 ◽  
Vol 9 (6) ◽  
pp. 769-774 ◽  
Author(s):  
L. D'Incerti ◽  
L. Farina ◽  
I. Moroni ◽  
G. Uziel ◽  
M. Savoiardo
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Subcortical White Matter ◽  
Neurological Damage ◽  
Biochemical Tests ◽  
Organic Acidurias ◽  
Basal Nuclei ◽  
Progressive Encephalopathy ◽  
Liver And Kidney ◽  
Neurological Features

Organic acidurias are congenital metabolic disorders variously involving the metabolic pathways, mainly the catabolism of aminoacids and fatty acids with accumulation of one or more organic acids in blood or urine. This group of diseases includes over 50 specific forms which, although rare, are the most common cause of acute encephalopathy in infancy. Single or recurrent episodes of metabolic failure are the most frequent presenting symptom in infancy, often in the first weeks of life. Onset may also occur later with features of chronic encephalopathy and complex clinical features including seizures, dystonia, hypotonia and in some cases myopathies associated with liver and kidney failure. Early diagnosis of acute forms is important since some organic acidurias can be treated thus preventing often fatal episodes of metabolic failure or ongoing neurological damage. Definitive diagnosis requires a search for pathological metabolites in urine using gas chromatography and mass spectroscopy and confirmation of enzyme deficit. Neurological investigation will show features indicative of metabolic disease in acute forms and in children presenting with progressive encephalopathy. Neurological features are heterogeneous, but MR findings will offer information for subsequent biochemical tests and sometimes suggest diagnosis, especially signal changes in the basal nuclei and subcortical white matter.

scholarly journals Neuroprotective Roles of the Reverse Transsulfuration Pathway in Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Bindu Diana Paul
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acids ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Review Article ◽  
Novel Treatments ◽  
Cellular Processes ◽  
Transsulfuration Pathway ◽  
Sulfur Containing

The reverse transsulfuration pathway has emerged as a central hub that integrates the metabolism of sulfur-containing amino acids and redox homeostasis. Transsulfuration involves the transfer of sulfur from homocysteine to cysteine. Cysteine serves as the precursor for several sulfur-containing molecules, which play diverse roles in cellular processes. Recent evidence shows that disruption of the flux through the pathway has deleterious consequences. In this review article, I will discuss the actions and regulation of the reverse transsulfuration pathway and its links to other metabolic pathways, which are disrupted in Alzheimer’s disease (AD). The potential nodes of therapeutic intervention are also discussed, which may pave the way for the development of novel treatments.

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