Advances in Type 2 Diabetes: Molecular Mechanisms and Therapeutic Innovations

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 1345

Special Issue Editor


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Guest Editor
Department of Medicine, University of Science, Arts and Technology, British West Indies, Montserrat, UK
Interests: type 2 diabetes mellitus; biophotonic treatment; obesity; metabolism; diabetes
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Special Issue Information

Dear Colleagues,

The prevalence of Type 2 diabetes is presently increasing at an alarming rate of near-epidemic proportions in numerous global populations, where it has a significant impact on available therapeutic and socioeconomic resources. This is in addition to the medical impact on human health and the impact it has on productivity for those individuals who develop the disorder.  Furthermore, type 2 diabetes is a significant public health concern due to its close link with numerous metabolic comorbidities, such as obesity and overweight conditions, dyslipidemia, renal dysfunction,  and cardiovascular disorders. Evidence suggests that heritable factors, in addition to excessive or inappropriate nutrient intake, contribute to the expression and development of insulin resistance and systemic inflammation, classic hallmarks of the disorder. Costly, long-term pharmacologic and dietary interventions remain the primary strategies for managing type 2 diabetes and its associated metabolic disorders. However,  current strategies seldom bring about curative, lasting results, indicating a need for more effective therapeutic measures likely focused at the molecular or epigenetic level are necessary. In this Special Issue, we plan to explore current advances in Type 2 diabetes, including nutritional factors, molecular mechanisms, sirtuins and other epigenetic factors, and emerging therapeutic innovations to address and resolve the rapidly increasing prevalence of Type 2 diabetes. Nutrient-dense, manufactured foods now represent over 50% of the daily caloric intake in some industrialized nations where Type 2 diabetes is prevalent, and while commercially processed foods are considered generally safe for human consumption, they typically contain greater amounts of dietary fats, salt and other chemical preservatives than wholesome fresh farm-to-table food choices, and pose a greater risk of premature demise when a high proportion of  industrialized food selections are consumed. The contributions of commercially manufactured food consumption to maintaining a healthy gut microbiota also remain unclear. 

In this Special Issue, we aim to cover aspects of molecular,  hormonal, epigenetic,  macro- and micro-nutrient, environmental, and socioeconomic significance, as well as the current dietary and pharmacotherapeutic recommendations. We plan to explore the primary metabolic pathways and molecular mechanisms in which each nutrient or dietary additive contributes a role, and their contribution to the development of Type 2 diabetes and its metabolic comorbidities. Importantly, gut microbiota are also crucial in regulating the metabolic responses to nutrient intake. As such, we also aim to gain a mechanistic understanding of how nutrients, intestinal microbiota and other factors may contribute to the metabolic health of the human host. By doing so, we hope to shed light on the pathogenesis of various common metabolic disorders including, but not limited to, type 2 diabetes, obesity, renal diseases, and cardiometabolic diseases. Thus, this Special Issue will focus on novel strategies, epigenetic mechanisms, and molecular mechanisms, as well as nutritional approaches, to address the ongoing increase in the prevalence of type 2 diabetes and its associated metabolic disturbances. With this, this Special Issue of Biomolecules, entitled “Advances in Type 2 Diabetes: Molecular Mechanisms and Therapeutic Innovations”, aims to solicit original research papers or review articles on the current state of research in this field, including both discovery and preclinical studies.

We look forward to receiving your contributions.

Dr. Orien L. Tulp
Guest Editor

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Keywords

  • type 2 diabetes (T2DM)
  • insulin resistance
  • GLUT4
  • sirtuins
  • epigenetic expression
  • nutrition
  • pharmacotherapeutics

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Published Papers (1 paper)

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Research

22 pages, 7811 KB  
Article
BDH1 Mediates Aerobic Exercise-Induced Improvement in Skeletal Muscle Metabolic Remodeling in Type 2 Diabetes Mellitus
by Mingyu Wu, Xiaotong Ma, Wei Dai, Ke Li, Haoyang Gao, Yifan Guo and Weihua Xiao
Biomolecules 2026, 16(1), 115; https://doi.org/10.3390/biom16010115 - 8 Jan 2026
Viewed by 962
Abstract
Background: Type 2 diabetes mellitus (T2DM) is typically characterized by the dysregulation of metabolic remodeling. As a systemic metabolic disease, T2DM can affect the mass and function of skeletal muscle by inducing impaired energy metabolism, mitochondrial dysfunction, and chronic low-grade inflammation. β-Hydroxybutyrate dehydrogenase [...] Read more.
Background: Type 2 diabetes mellitus (T2DM) is typically characterized by the dysregulation of metabolic remodeling. As a systemic metabolic disease, T2DM can affect the mass and function of skeletal muscle by inducing impaired energy metabolism, mitochondrial dysfunction, and chronic low-grade inflammation. β-Hydroxybutyrate dehydrogenase 1 (BDH1) is a rate-limiting enzyme involved in ketone body metabolism, and its activity is down-regulated in various models of diabetic complications. Aerobic exercise (AE) is recognized as an effective intervention to promote energy homeostasis and alleviate metabolic stress. Whether its protective effect on skeletal muscle in T2DM involves the regulatory control of BDH1 expression remains unclear. Methods: Wild-type (WT) and systemic BDH1 knockout (BDH1−/−) male C57BL/6J mice were used to establish the sedentary control (SED) and AE models of T2DM by providing a high-fat diet combined with streptozotocin injection. The indicators related to metabolic remodeling were detected by hematoxylin and eosin staining, immunofluorescence staining, quantitative real-time PCR, and Western blot assays. Results: After 8 weeks of AE, we found that AE improved glycolipid metabolic disorders and mitochondrial quality control in the gastrocnemius muscle of T2DM mice by up-regulating BDH1, thereby alleviating oxidative stress, inflammation, and fibrosis. Compared with the WT mice, the BDH1−/− T2DM mice in the SED group exhibited more severe phenotypic impairment. The metabolic improvement effect of AE was attenuated in the BDH1−/− mice. Conclusions: BDH1 is a key effector enzyme that may mediate the AE-induced improvement in metabolic remodeling in the gastrocnemius muscle of mice with T2DM. Full article
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