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Molecular Insights in Diabetes

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: 20 June 2026 | Viewed by 2575

Special Issue Editors


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Guest Editor
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Interests: lipid metabolism; familial hypercholesterolemia; inherited dyslipidemias; atherosclerosis; non-lipid effects of lipid lowering treatment; obesity; diabetes
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Interests: diabetes mellitus; oxidative stress; atherosclerosis; diabetic neuropathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Type 2 diabetes is characterised by a complex pathophysiology involving impaired insulin action, beta-cell dysfunction, and increased oxidative stress. There is extensive scientific evidence demonstrating that impaired insulin signalling leads to impaired glucose uptake and insulin resistance. Furthermore, inflammatory pathways and oxidative damage exacerbate insulin resistance, contributing to the development of microvascular and cardiovascular complications. Epigenetic changes, such as DNA methylation and histone modifications, can cause long-term shifts in gene expression, even after glycaemic control is achieved—a phenomenon known as 'metabolic memory'. Additionally, microRNAs and other non-coding RNAs play a pivotal role in maintaining beta-cell function, and their dysregulation has been associated with disease progression. The therapeutic use of gut-derived hormones (including incretins such as GLP-1 and GIP) that target these pathways offers a novel means of restoring glucose homeostasis. This Special Issue invites original research and reviews focusing on molecular mechanisms, regulatory RNAs, epigenetic memory, and innovative therapies. We welcome contributions that explore how emerging science can improve treatment outcomes and expand our understanding of the pathophysiology of type 2 diabetes.

Dr. Mariann Harangi
Dr. Ferenc Sztanek
Guest Editors

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Keywords

  • insulin signalling pathway
  • pancreatic beta-cell dysfunction
  • oxidative stress
  • epigenetic modifications
  • metabolic memory
  • small regulatory RNAs (miRNAs)
  • inflammation and insulin resistance
  • glucagon-like peptide-1 (GLP-1)
  • glucose-dependent insulinotropic polypeptide (GIP)
  • molecular therapeutic targets
  • glucose homeostasis regulation

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Published Papers (2 papers)

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Review

22 pages, 1291 KB  
Review
Modulatory Effects of Polyphenols on Altered Leukocyte Functions in Thromboinflammation and Diabetes Mellitus
by Dina Muharib, Xinyi Wu, Christine Boesch, Robert A. S. Ariëns and Julia S. Gauer
Int. J. Mol. Sci. 2026, 27(8), 3585; https://doi.org/10.3390/ijms27083585 - 17 Apr 2026
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Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent low-grade inflammation and a markedly increased risk of cardiovascular diseases (CVD). Leukocytes play an important role not only in host defense but are also increasingly recognized as key contributors to haemostasis and [...] Read more.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent low-grade inflammation and a markedly increased risk of cardiovascular diseases (CVD). Leukocytes play an important role not only in host defense but are also increasingly recognized as key contributors to haemostasis and thromboinflammatory processes. In DM, chronic hyperglycaemia, oxidative stress and inflammation lead to leukocyte dysfunction, including enhanced cell activation, impaired mitochondrial function, and dysregulated interactions with platelets and endothelial cells. These alterations promote the thromboinflammatory state that contributes to vascular complications in DM. Thus, the modulation of oxidative stress and inflammation are important. Polyphenols are a class of plant secondary metabolites widely studied for their antioxidant and anti-inflammatory properties. This review comprehensively explores leukocyte dysfunction in DM, its contribution to thromboinflammation, and the mechanistic role of polyphenols in modulating these processes. The evidence presented suggests that polyphenols may contribute to the modulation of thromboinflammatory pathways. Further research in this area is required to enhance our understanding of thromboinflammation in DM and to translate these findings into effective adjunctive strategies, alongside standard pharmacological therapies to reduce CVD risk in individuals with DM. Full article
(This article belongs to the Special Issue Molecular Insights in Diabetes)
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20 pages, 1522 KB  
Review
Semaglutide-Mediated Remodeling of Adipose Tissue in Type 2 Diabetes: Molecular Mechanisms Beyond Glycemic Control
by Tatjana Ábel and Éva Csobod Csajbókné
Int. J. Mol. Sci. 2026, 27(3), 1186; https://doi.org/10.3390/ijms27031186 - 24 Jan 2026
Cited by 1 | Viewed by 1845
Abstract
Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development [...] Read more.
Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Molecular Insights in Diabetes)
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