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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: 30 June 2025 | Viewed by 571

Special Issue Editor

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

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Keywords

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

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Published Papers (1 paper)

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Research

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 201
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
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