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Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0
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Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0

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

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 5473

Special Issue Editors

Dr. Cosmin Mihai Vesa

E-Mail Website
Guest Editor
Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Interests: sustainability in public health; occupational medicine; environment-associated diseases; sick building syndrome; one health
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Simona Gabriela Bungau

E-Mail Website
Guest Editor
Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
Interests: medicine; pharmacology; antidiabetic drugs; metabolism; public health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

The purpose of this issue is to present the impact in clinical practice as well as in medical research of novel molecules that have been introduced in the treatment of diabetes mellitus, dyslipidemia, and cardiovascular disease. The topic focuses on the improvements in disease outcomes as well as the numerous beneficial effects of use of certain medications such as GLP-1 agonists, dual GLP-1/ GIP agonists, and SGLT-2 inhibitors for diabetes mellitus treatment; PCSK9 inhibitors and small interfering RNA (siRNA) molecules for dyslipidemia; and antiaggregants, oral anticoagulants, scubitril/valsartan, and non-steroidal mineralocorticoid receptor agonists or dapagliflozin in cardiovascular diseases. We believe that the number of real-life studies and in vivo and in vitro research of the effects of these drugs is quite low at the moment, leading to a lack of understanding of the complex molecular effects and pleiotropic effects of these medications, as well as incomplete knowledge regarding the repurposing of these drugs in clinical practice. Thus, this Special Issue is incredibly topical and important, and we look forward to your submissions which will help to clarify the issues surrounding such drugs.

Dr. Cosmin Mihai Vesa
Prof. Dr. Simona Gabriela Bungau
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

  • GLP-1 agonists
  • GLP-1/GIP agonists
  • SGLT-2 inhibitors
  • dyslipidemia
  • PCSK9 inhibitors
  • diabetes mellitus
  • sacubitril/valsartan
  • small interfering RNA (siRNA) molecules for dyslipidemia
  • novel oral anticoagulants
  • non-steroidal MRA
  • cardiovascular disease

Published Papers (6 papers)

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Research

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12 pages, 515 KiB  
Article
Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population
by Dominik Franciszek Dłuski, Marek Cieśla and Dorota Darmochwał-Kolarz
Int. J. Mol. Sci. 2024, 25(13), 7040; https://doi.org/10.3390/ijms25137040 - 27 Jun 2024
Viewed by 168
Abstract
Gestational diabetes mellitus (GDM) is an intolerance of carbohydrate of any degree, which appears for the first time or is diagnosed during pregnancy. The objective of this study is to assess the differences in circular RNA (circRNA) in a Polish pregnant population with [...] Read more.
Gestational diabetes mellitus (GDM) is an intolerance of carbohydrate of any degree, which appears for the first time or is diagnosed during pregnancy. The objective of this study is to assess the differences in circular RNA (circRNA) in a Polish pregnant population with and without GDM. A total of 62 pregnant women, 34 with GDM and 28 controls, were enrolled in the study. Total RNAs were extracted from plasma and reverse transcription to complementary DNA (cDNA) was performed. A panel covering 271 amplicons, targeting both linear and circular as well as negative control gene transcripts, was used. Next-generation sequencing was used to evaluate the circRNA quantity. Data analysis was performed using the Coverage Analysis plugin in the Torrent Suite Software (Torrent Suite 5.12.3). A two-step normalization was performed by dividing each transcript read count by the total number of reads generated for the sample, followed by dividing the quantity of each transcript by β-actin gene expression. Both circular and linear forms of RNAs were independently evaluated. A total of 57 transcripts were dysregulated between pregnant women with GDM and controls. Most of the targets (n = 25) were downregulated (cut-off ratio below 0.5), and one target showed a trend toward strong upregulation (ratio 1.45). A total of 39 targets were positively correlated with fasting plasma glucose (FPG), but none of the tested targets were correlated with insulin, CRP or HOMA-IR levels. Among the pregnant women with gestational diabetes, the relative quantity of hsa_circ_0002268 (PHACTR1) was approximately 120% higher than among healthy pregnant women: 0.046 [0.022–0.096] vs. 0.021 [0.007–0.047], respectively, (p = 0.0029). Elevated levels of hsa_circ_0002268 (PHACTR1) might be specific to the Polish population of pregnant women with GDM, making it useful as a potential molecular biomarker in the management of GDM in Poland. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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13 pages, 2050 KiB  
Article
Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human
by Alexandra Höpfinger, Andreas Schmid, Thomas Karrasch, Sabine Pankuweit, Andreas Schäffler and Karsten Grote
Int. J. Mol. Sci. 2024, 25(5), 2909; https://doi.org/10.3390/ijms25052909 - 2 Mar 2024
Viewed by 803
Abstract
Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate [...] Read more.
Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate immune system and metabolism in these settings. We investigated systemic CAMP/CRAMP levels in experimental murine models of atherosclerosis, myocardial infarction and cardiovascular patients. Atherosclerosis was induced in low-density lipoprotein receptor-deficient (Ldlr−/−) mice by high-fat diet (HFD). C57BL/6J wild-type mice were subjected to myocardial infarction by permanent or transient left anterior descending (LAD)-ligation. Cramp gene expression in murine organs and tissues was investigated via real-time PCR. Blood samples of 234 adult individuals with or without coronary artery disease (CAD) were collected. Human and murine CAMP/CRAMP serum levels were quantified by ELISA. Atherosclerotic mice exhibited significantly increased CRAMP serum levels and induced Cramp gene expression in the spleen and liver, whereas experimental myocardial infarction substantially decreased CRAMP serum levels. Human CAMP serum quantities were not significantly affected by CAD while being correlated with leukocytes and pro-inflammatory cytokines. Our data show an influence of cathelicidin in experimental atherosclerosis, myocardial infarction, as well as in patients with CAD. Further studies are needed to elucidate the pathophysiological mechanism. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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Review

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18 pages, 1635 KiB  
Review
Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes
by Stéphane Dalle
Int. J. Mol. Sci. 2024, 25(12), 6425; https://doi.org/10.3390/ijms25126425 - 11 Jun 2024
Viewed by 458
Abstract
The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass characterizes type 2 diabetes. To date, none of the available antidiabetic drugs promotes the maintenance of a functional mass of [...] Read more.
The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass characterizes type 2 diabetes. To date, none of the available antidiabetic drugs promotes the maintenance of a functional mass of endogenous beta-cells, revealing an unmet medical need. Dysfunction and apoptotic death of beta-cells occur, in particular, through the activation of intracellular protein kinases. In recent years, protein kinases have become highly studied targets of the pharmaceutical industry for drug development. A number of drugs that inhibit protein kinases have been approved for the treatment of cancers. The question of whether safe drugs that inhibit protein kinase activity can be developed and used to protect the function and survival of beta-cells in diabetes is still unresolved. This review presents arguments suggesting that several protein kinases in beta-cells may represent targets of interest for the development of drugs to treat diabetes. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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28 pages, 1160 KiB  
Review
New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions
by Kyriazoula Chatzianagnostou, Melania Gaggini, Adrian Suman Florentin, Ludovica Simonini and Cristina Vassalle
Int. J. Mol. Sci. 2024, 25(11), 6218; https://doi.org/10.3390/ijms25116218 - 5 Jun 2024
Viewed by 431
Abstract
Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic [...] Read more.
Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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22 pages, 1630 KiB  
Review
The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis
by Teodora Bianca Sirca, Mariana Eugenia Mureșan, Annamaria Pallag, Eleonora Marian, Tunde Jurca, Laura Grațiela Vicaș, Ioana Paula Tunduc, Felicia Manole and Liana Ștefan
Int. J. Mol. Sci. 2024, 25(5), 2962; https://doi.org/10.3390/ijms25052962 - 4 Mar 2024
Cited by 1 | Viewed by 1094
Abstract
The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory [...] Read more.
The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), and high serum levels lead to a protective state against dyslipidemia, cardiovascular diseases, diabetes, stroke, nonalcoholic fatty liver disease, and many others. Modulating PON1 expression might be a treatment objective with significant results in limiting the prevalence of atherosclerosis. Lifestyle including diet and exercise can raise its levels, and some beneficial plants have been found to influence PON1 levels; therefore, more studies on herbal components are needed. Our purpose is to highlight the principal roles of Praoxonase 1, its implications in dyslipidemia, cardiovascular diseases, stroke, and other diseases, and to emphasize plants that can modulate PON1 expression, targeting the potential of some flavonoids that could be introduced as supplements in our diet and to validate the hypothesis that flavonoids have any effects regarding PON1 function. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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25 pages, 1824 KiB  
Review
Cardiometabolic Risk: Characteristics of the Intestinal Microbiome and the Role of Polyphenols
by Ioana Mariana Haș, Delia Mirela Tit, Simona Gabriela Bungau, Flavia Maria Pavel, Bernadette-Emoke Teleky, Dan Cristian Vodnar and Cosmin Mihai Vesa
Int. J. Mol. Sci. 2023, 24(18), 13757; https://doi.org/10.3390/ijms241813757 - 6 Sep 2023
Cited by 2 | Viewed by 1400
Abstract
Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols [...] Read more.
Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols are primarily known for their anti-inflammatory and antioxidant properties, but they can also modify the gut microbiota. According to recent research, polyphenols positively influence the gut microbiota, which regulates metabolic responses and reduces systemic inflammation. This review emphasizes the prebiotic role of polyphenols and their impact on specific gut microbiota components in patients at cardiometabolic risk. It also analyzes the most recent research on the positive effects of polyphenols on cardiometabolic health. While numerous in vitro and in vivo studies have shown the interaction involving polyphenols and gut microbiota, additional clinical investigations are required to assess this effect in people. Full article
(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)
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