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Molecular Therapeutics for Diabetes and Related Complications, 2nd Edition
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Molecular Therapeutics for Diabetes and Related Complications, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 March 2026 | Viewed by 1367

Special Issue Editor

Dr. Kota V. Ramana

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Interests: oxidative stress-induced signal transduction mechanisms; pathophysiology of secondary diabetic complications; carcinogenesis; inflammatory complications; therapeutic development of small molecular inhibitors and antioxidants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes poses a significant threat to global health, demanding attention due to its escalating prevalence and associated complications. Conventional treatments, such as insulin therapy, alongside newer glucose-lowering medications such as metformin, GLP-1 receptor agonists, SGLT-2 inhibitors, and insulin sensitizers, offer some effectiveness; however, they are also associated with some unwanted side effects, which necessitates the further exploration of novel therapeutic options. Worldwide, healthcare costs of this pathology increase every year, and there is a need to discover novel drug targets and molecular pathways for managing diabetes and its associated complications, such as diabetic nephropathy, retinopathy, neuropathy, and cardiovascular diseases. These targets not only promise to ameliorate diabetes but also offer avenues for mitigating the associated complications. Connecting these novel pathways will help to surpass the benefits of conventional therapies, thereby reducing the morbidity and mortality linked with diabetic complications. While recent preclinical studies have identified promising molecular pathways and targets, further clinical trials are needed in order to translate these findings into clinical practice. Additionally, research continues to explore means of reducing oxidative stress; enhancing antioxidant status; manipulating molecular and metabolic pathways using the innate immune response; and exploring microRNAs, stem cell therapy, and gene therapy as potential diagnostic and therapeutic tools. Thus, while conventional therapies remain crucial, the pursuit of novel molecular therapeutics holds promise regarding revolutionizing diabetes management and improving patient outcomes. This Special Issue aims to compile state-of-the-art insights into the role of novel molecular therapeutics in ameliorating diabetes and related complications and welcomes the submission of original research and review articles addressing all aspects of molecular and cellular pathways, therapeutic drug development, biomarker identification and verification, novel techniques, and computational, structural, and functional studies in the field of diabetes and its complications.

Dr. Kota V. Ramana
Guest Editor

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

  • diabetes
  • diabetes complications
  • molecular therapeutics
  • drug development
  • hyperglycemia
  • insulin resistance
  • cell signaling and oxidative stress

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Related Special Issue

Published Papers (2 papers)

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23 pages, 24539 KiB  
Article
NPC86 Increases LncRNA Gas5 In Vivo to Improve Insulin Sensitivity and Metabolic Function in Diet-Induced Obese Diabetic Mouse Model
by Anna Kharitonova, Rekha S. Patel, Brenna Osborne, Meredith Krause-Hauch, Ashley Lui, Gitanjali Vidyarthi, Sihao Li, Jianfeng Cai and Niketa A. Patel
Int. J. Mol. Sci. 2025, 26(8), 3695; https://doi.org/10.3390/ijms26083695 - 14 Apr 2025
Viewed by 576
Abstract
In the United States, an estimated 38 million individuals (10% of the population) have type 2 diabetes mellitus (T2D), while approximately 97.6 million adults (38%) have prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators of gene expression and metabolism. We were the first [...] Read more.
In the United States, an estimated 38 million individuals (10% of the population) have type 2 diabetes mellitus (T2D), while approximately 97.6 million adults (38%) have prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators of gene expression and metabolism. We were the first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in the serum of T2D patients and established GAS5 as a biomarker for T2D diagnosis and onset prediction, now validated by other groups. We further demonstrated that GAS5 depletion impaired glucose uptake, decreased insulin receptor levels, and inhibited insulin signaling in human adipocytes, highlighting its potential as a therapeutic target in T2D. To address this, we developed NPC86, a small-molecule compound that stabilizes GAS5 by disrupting its interaction with UPF-1, an RNA helicase involved in nonsense-mediated decay (NMD) that regulates RNA stability. NPC86 increased GAS5 and insulin receptor (IR) levels, enhanced insulin signaling, and improved glucose uptake in vitro. In this study, we tested the efficacy of NPC86 in vivo in a diet-induced obese diabetic (DIOD) mouse model, and NPC86 treatment elevated gas5 levels, improved glucose tolerance, and enhanced insulin sensitivity, with no observed toxicity or weight changes. A transcriptomics analysis of adipose tissue revealed the upregulation of insulin signaling and metabolic pathways, including oxidative phosphorylation and glycolysis, while inflammatory pathways were downregulated. These findings highlight NPC86’s therapeutic potential in T2D. Full article
(This article belongs to the Special Issue Molecular Therapeutics for Diabetes and Related Complications, 2nd Edition)
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30 pages, 1486 KiB  
Systematic Review
Comparison of the Mediterranean Diet and Other Therapeutic Strategies in Metabolic Syndrome: A Systematic Review and Meta-Analysis
by Alejandro Bruna-Mejias, Jessica San Martin, Danna Arciniegas-Diaz, Trinidad Meneses-Caroca, Amelia Salamanca-Cerda, Antonia Beas-Gambi, Jessica Paola-Loaiza-Giraldo, Cynthia Ortiz-Ahumada, Pablo Nova-Baeza, Gustavo Oyanedel-Amaro, Mathias Orellana-Donoso, Alejandra Suazo-Santibáñez, Juan Sanchis-Gimeno and Juan José Valenzuela-Fuenzalida
Int. J. Mol. Sci. 2025, 26(12), 5887; https://doi.org/10.3390/ijms26125887 - 19 Jun 2025
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Abstract
The Mediterranean diet (MD) is one of the healthiest diets, high in fiber, antioxidants, and unsaturated fats. MD improves lipid profiles, reduces inflammation, controls blood pressure, decreases insulin resistance, and enhances the sensitivity to this hormone, lowering the risks of Metabolic syndrome (MS). [...] Read more.
The Mediterranean diet (MD) is one of the healthiest diets, high in fiber, antioxidants, and unsaturated fats. MD improves lipid profiles, reduces inflammation, controls blood pressure, decreases insulin resistance, and enhances the sensitivity to this hormone, lowering the risks of Metabolic syndrome (MS). MS is characterized by central obesity, hypertension, insulin resistance, and dyslipidemia, increasing the risk of cardiovascular disease and type II diabetes. The objective of this study was to know the effectiveness of the MD versus other treatments in patients with MS. A systematic search across multiple databases, Medline, Embase, Web of Science, Scopus, Google Scholar, and Cinahl, was conducted using keywords such as “Mediterranean diet”, “Mediterranean food”, “eat mediterranean”, “Metabolic syndrome”, and “x syndrome”. A total of 12 studies met the inclusion criteria. Mediterranean diet at different doses versus other diets or other treatments showed significant improvements in clinical parameters, including BMI (mean difference of −0.83 95% CI: −0.93 to −0.74; p < 0.00001),waist circumference (mean difference = −1.81, CI = −2.63 to −0.99, p < 0.00001) triglycerides (mean difference = −22.38, CI = −32.86 to −11.90, p < 0.00001), Glucose (mean difference = −4.28, CI = −7.64 to −0.93, p = 0.005) and, HOMA IR (mean difference = −0.72, CI = −0.78 to −0.65, p < 0.00001), and Insulin resistance (mean difference = −2.98, CI = −3.27 to −2.69, p < 0.00001), all of which improved, Although there were more outcomes, these are the most important changes for patients with metabolic syndrome. MD improves metabolic and cardiovascular health, but study heterogeneity limits the results’ generalizability. Because of that, further research is needed to standardize approaches and explore their mechanisms. MD should be part of an optimized strategy that includes education and physical activity. The strength of the evidence was very low according to the GRADE approach. Further research is needed to support the efficacy of the Mediterranean diet in patients with MS. Full article
(This article belongs to the Special Issue Molecular Therapeutics for Diabetes and Related Complications, 2nd Edition)
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