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Molecular Mechanism of Diabetes and Its Complications

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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 (20 April 2026) | Viewed by 7418

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Dr. Michishige Terasaki

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Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-0064, Japan
Interests: macrophage; diabetic comorbidities; atherosclerosis
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Dear Colleagues,

Diabetes increases the risk of comorbidities, such as retinopathy, neuropathy, nephropathy, coronary artery disease, peripheral artery disease, and stroke. Various biochemical pathways activated under hyperglycemic conditions can contribute to the complications. It is important to reveal the mechanisms of early characteristic features of the comorbidities in hyperglycemia, which is considered to have a principal role in accelerating complications. For this Special Issue, we invite original research, review articles, rare case reports, and literature reviews on recent progress in molecular mechanisms of the relationship of diabetes with the complications in humans and animals.

Dr. Michishige Terasaki
Guest Editor

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Keywords

diabetes
hyperglycemia
oxidative stress
atherosclerosis
comorbidity
complication
metabolic metabolic dysfunction associated steatotic liver disease (MASLD)
steatohepatitis (MASH)
chronic kidney disease (CKD)
heart failure
heart failure with preserved ejection fraction (HFpEF)
coronary artery disease (CAD)

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Published Papers (4 papers)

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Research

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25 pages, 1195 KB

Open AccessArticle

Metabolic Dysregulation, Inflammation, and Median Nerve Dysfunction in Patients with Type 2 Diabetes Mellitus with Carpal Tunnel Syndrome

by Adina Stoian, Simona Cernea, Claudia Bănescu, Mircea Stoian, Andrei Manea, Florina Gliga, Dumitru Golban, Andrei Stîngaciu and Rodica Bălașa

Int. J. Mol. Sci. 2026, 27(11), 4995; https://doi.org/10.3390/ijms27114995 - 30 May 2026

Cited by 1 | Viewed by 1455

Abstract

Carpal tunnel syndrome (CTS) is the most common compressive mononeuropathy. In patients with type 2 diabetes mellitus (T2DM), chronic hyperglycemia, microangiopathy, and systemic inflammation increase the vulnerability of peripheral nerves to compression. This study aimed to assess the relationship between CTS severity and clinical, metabolic, inflammatory, and electrophysiological parameters in patients with T2DM. A cross-sectional study was conducted from June 2023 to June 2024, involving patients diagnosed with T2DM. Electrophysiological assessment of the upper and lower limbs was performed using a four-channel electromyography apparatus. Clinical and anthropometric data and laboratory parameters were obtained, as well as the results of nerve conduction studies (NCS). One hundred and twenty-three patients with T2DM were included in the study. The prevalence of moderate-to-severe forms of CTS was 43.9%, and bilateral involvement was present in 21.95% of patients. Patients with moderate-to-severe CTS had significantly higher hemoglobin A1c (HbA1c) (p = 0.004), glycemia (p < 0.001), and Triglyceride–Glucose Index (p = 0.018) compared with those without CTS/with mild forms. The number of monocytes was significantly higher in the group with moderate-to-severe forms (p = 0.012), suggesting a chronic inflammatory state. In the logistic regression analysis, hemoglobin HbA1c emerged as an independent predictor of CTS severity, with each 1% increase associated with approximately a 60% higher risk of moderate/severe CTS. NCS analysis showed significant correlations between median nerve parameters and those of the lower-limb peripheral nerves, particularly the tibial and sural nerves, suggesting an association with generalized diabetic peripheral neuropathy. Professional activity was significantly associated with moderate-to-severe CTS (OR = 3.5). CTS is a common complication in patients with T2DM and is associated with worse glycemic control, insulin resistance, systemic inflammation, and peripheral neuropathic damage. Full article

(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)

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10 pages, 1360 KB

Open AccessArticle

The Role of Oxidative Stress in the Effect of Quercetin on Na⁺/K⁺-ATPase Expression in Skeletal Muscle in a Metabolic Syndrome Model

by Ayca Bilginoglu Topcu

Int. J. Mol. Sci. 2026, 27(10), 4369; https://doi.org/10.3390/ijms27104369 - 14 May 2026

Viewed by 329

Abstract

Metabolic syndrome (MeS) is a multifactorial disorder characterized by insulin resistance, dyslipidemia, hypertension, and obesity, and oxidative stress plays a key role in tissue damage in this syndrome. This study aimed to investigate this role in Na⁺/K⁺-ATPase (NKA) expression in skeletal muscle and to evaluate the effects of quercetin. A high-sucrose-diet-induced MeS model was established in Wistar albino rats (n = 32), and skeletal muscle tissues were analyzed. Biochemical parameters were measured, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), and malondialdehyde (MDA). In addition, thioredoxin-1 (TRX1) and NKA protein expression levels were evaluated using Western blot analysis. In the MeS group, AST, TAS, TRX1, and NKA expression significantly decreased, while LDH, TOS, SOD, and MDA levels increased, indicating disrupted redox balance, elevated oxidative stress, and impaired antioxidant defense. Increased MDA and TOS levels reflected enhanced lipid peroxidation, whereas decreased TAS and TRX1 suggested reduced antioxidant capacity. Elevated SOD activity may indicate a compensatory response to excessive reactive oxygen species (ROS). The reduction in NKA expression may contribute to impaired ion transport and potential skeletal muscle dysfunction. Quercetin administration improved oxidative stress markers and partially restored NKA expression. These findings suggest that oxidative stress contributes to NKA dysfunction in MeS, and quercetin may have therapeutic potential by modulating oxidative stress and preserving enzyme function. Full article

(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)

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28 pages, 10095 KB

Open AccessReview

Gymnema sylvestre as a Multi-Target Antidiabetic Agent: Mechanistic Insights and Metabolic Regulation

by Sedef Ziyanok-Demirtas and Irem Serin

Int. J. Mol. Sci. 2026, 27(12), 5609; https://doi.org/10.3390/ijms27125609 - 22 Jun 2026

Viewed by 1346

Abstract

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article

(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)

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53 pages, 3624 KB

Open AccessReview

Photobiomodulation and Low-Level Laser Therapy as Complementary Strategies in Diabetes Treatment

by Natalia Kurhaluk, Vladimir Tomin, Renata Kołodziejska and Halina Tkaczenko

Int. J. Mol. Sci. 2026, 27(4), 2078; https://doi.org/10.3390/ijms27042078 - 23 Feb 2026

Cited by 3 | Viewed by 3501

Abstract

Diabetes mellitus is a multifactorial metabolic disorder associated with a number of chronic complications, including neuropathy, impaired wound healing, vascular dysfunction, and metabolic dysregulation. Despite advances in pharmacological treatments and lifestyle interventions, current therapies often fail to prevent or reverse these complications entirely. This narrative review examines the therapeutic potential of laser-based modalities, particularly low-level laser therapy (LLLT) and photobiomodulation therapy (PBMT), as complementary strategies in diabetes management. Analysis of experimental and clinical studies shows that laser therapy can enhance wound healing, alleviate neuropathic pain, improve glycaemic control and insulin sensitivity, modulate inflammatory and oxidative stress pathways, and support vascular function. These effects are primarily mediated through mitochondrial activation, nitric oxide release, angiogenesis, modulation of redox-sensitive transcription factors, and preservation of pancreatic β-cell function. Furthermore, laser therapy exhibits a favourable safety profile with minimal side effects. The review highlights the current challenges, such as the lack of standardised treatment parameters (e.g., wavelength, dosage, and duration) and the limited number of large-scale clinical trials. It emphasises the need for personalised protocols and integration of laser therapy with pharmacological and physiotherapeutic interventions. Continued research and interdisciplinary collaboration are needed to realise the potential of laser therapy as an integral component of comprehensive, evidence-based diabetes care. Full article

(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)

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