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Pharmacological Strategies for Metabolic Diseases: New Evidence

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 14355

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Special Issue Editors

Dr. Elisa Benetti

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Guest Editor

Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via Pietro Giuria 9, 10125 Turin, Italy
Interests: type 2 diabetes; inflammation; insulin resistance; NLRP3 inflammasome
Special Issues, Collections and Topics in MDPI journals

Dr. Gemma K. Kinsella

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Guest Editor

School of Food Science & Environmental Health, Technological University Dublin, D07 ADY7 Dublin 1, Ireland
Interests: type 2 diabetes; anti-diabetic drugs; cancer therapeutics; protein modelling; molecular docking; virtual screening

Special Issue Information

Dear Colleagues,

Metabolic diseases, whether caused by genetic or non-genetic factors, impair normal cell metabolism by affecting the processing or the transport of lipids, carbohydrates or proteins. Current therapeutic treatments aim to restore normal physiological conditions. However, in some cases therapeutic agents are lacking and treatments are targeted at controlling patient symptoms. In other cases, despite numerous therapeutic strategies being available, some patients are still unable to achieve the therapeutic goal, thus highlighting the ongoing need to optimize the therapeutic options.

This Special Issue will focus on the latest advances in pharmacological strategies for the treatment of metabolic diseases. Particularly welcome will be original research articles on metabolic diseases providing (i) new evidence about known molecular targets or pharmacological strategies (new insights on molecular mechanism, adverse events, pleiotropic actions etc..) (ii) Identification of new molecular targets or novel pharmacological strategies of potential interest.

Dr. Elisa Benetti
Dr. Gemma K. Kinsella
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

metabolic diseases
pharmacology
molecular targets
type 2 diabetes

Published Papers (4 papers)

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Research

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14 pages, 3056 KiB

Open AccessArticle

GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells

by Gemma K. Kinsella, Stefania Cannito, Valentina Bordano, John C. Stephens, Arianna C. Rosa, Gianluca Miglio, Valeria Guaschino, Valeria Iannaccone, John B.C. Findlay and Elisa Benetti

Int. J. Mol. Sci. 2021, 22(19), 10784; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910784 - 05 Oct 2021

Cited by 4 | Viewed by 2777

Abstract

GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was to examine the role of GPR21 in the regulation of glucose uptake and production in human hepatocytes. In particular, HepG2 cells, which express GPR21, were adopted as cellular models. Compared with untreated cells, a significant increase in glucose uptake was measured in cells treated with siRNA to downregulate GPR21 expression or with the GPR21-inverse agonist, GRA2. Consistently, a significantly higher membrane translocation of GLUT-2 was measured under these conditions. These effects were accompanied by an increased ratio of phAKT^(Ser473)/tot-AKT and phGSK-3β^(Ser9)/tot-GSK-3β, thus indicating a marked activation of the insulin signalling pathway. Moreover, a significant reduction in ERK activation was observed with GPR21 inhibition. Collectively, these results indicate that GPR21 mediates the negative effects on glucose uptake by the liver cells. In addition, they suggest that the pharmacological inhibition of GPR21 could be a novel strategy to improve glucose homeostasis and counteract hepatic insulin resistance. Full article

(This article belongs to the Special Issue Pharmacological Strategies for Metabolic Diseases: New Evidence)

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Review

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18 pages, 617 KiB

Open AccessReview

Therapy of Type 2 Diabetes in Patients with SARS-CoV-2 Infection

by Weronika Bielka, Agnieszka Przezak and Andrzej Pawlik

Int. J. Mol. Sci. 2021, 22(14), 7605; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147605 - 16 Jul 2021

Cited by 16 | Viewed by 2821

Abstract

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes. Full article

(This article belongs to the Special Issue Pharmacological Strategies for Metabolic Diseases: New Evidence)

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18 pages, 737 KiB

Open AccessReview

Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity

by Lucy Darakjian, Malavika Deodhar, Jacques Turgeon and Veronique Michaud

Int. J. Mol. Sci. 2021, 22(9), 4967; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094967 - 07 May 2021

Cited by 32 | Viewed by 3766

Abstract

Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens. Full article

(This article belongs to the Special Issue Pharmacological Strategies for Metabolic Diseases: New Evidence)

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28 pages, 2522 KiB

Open AccessReview

Diabetes Mellitus Is a Chronic Disease that Can Benefit from Therapy with Induced Pluripotent Stem Cells

by Felipe Arroyave, Diana Montaño and Fernando Lizcano

Int. J. Mol. Sci. 2020, 21(22), 8685; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228685 - 18 Nov 2020

Cited by 12 | Viewed by 4316

Abstract

Diabetes mellitus (DM) is one of the main causes of morbidity and mortality, with an increasing incidence worldwide. The impact of DM on public health in developing countries has triggered alarm due to the exaggerated costs of the treatment and monitoring of patients with this disease. Considerable efforts have been made to try to prevent the onset and reduce the complications of DM. However, because insulin-producing pancreatic β-cells progressively deteriorate, many people must receive insulin through subcutaneous injection. Additionally, current therapies do not have consistent results regarding the prevention of chronic complications. Leveraging the approval of real-time continuous glucose monitors and sophisticated algorithms that partially automate insulin infusion pumps has improved glycemic control, decreasing the burden of diabetes management. However, these advances are facing physiologic barriers. New findings in molecular and cellular biology have produced an extraordinary advancement in tissue development for the treatment of DM. Obtaining pancreatic β-cells from somatic cells is a great resource that currently exists for patients with DM. Although this therapeutic option has great prospects for patients, some challenges remain for this therapeutic plan to be used clinically. The purpose of this review is to describe the new techniques in cell biology and regenerative medicine as possible treatments for DM. In particular, this review highlights the origin of induced pluripotent cells (iPSCs) and how they have begun to emerge as a regenerative treatment that may mitigate the pathology of this disease. Full article

(This article belongs to the Special Issue Pharmacological Strategies for Metabolic Diseases: New Evidence)

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