Advanced Approaches in Immunotherapy for the Treatment of Type 1 Diabetes Mellitus

Ceballos, Bryan; Alexander, Michael P.; Lakey, Jonathan R.T.

doi:10.33590/emjdiabet/20-00062

Cited by 2 publications

(1 citation statement)

References 78 publications

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“…Recent advances in metabolomics, transgenic mice and immunometabolism have shown that metabolic adaptation plays a crucial role in shaping T cell responses (12)(13)(14). T cell activation is linked to metabolic reprogramming to meet the increased energy and biomass demand (15,16).…”

Section: Introductionmentioning

confidence: 99%

New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes

et al. 2022

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Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells and is becoming a serious public health threat. Despite the increasing incidence rate of T1D worldwide, our understanding of why T1D develops and how T cells lose their self-tolerance in this process remain limited. Recent advances in immunometabolism have shown that cellular metabolism plays a fundamental role in shaping T cell responses. T cell activation and proliferation are supported by metabolic reprogramming to meet the increased energy and biomass demand, and deregulation in immune metabolism can lead to autoimmune disorders. Specific metabolic pathways and factors have been investigated to rectify known deficiencies in several autoimmune diseases, including T1D. Most therapeutic strategies have concentrated on aerobic glycolysis to limit T cell responses, whereas glycolysis is the main metabolic pathway for T cell activation and proliferation. The use of metabolic inhibitors, especially glycolysis inhibitors may largely leave T cell function intact but primarily target those autoreactive T cells with hyperactivated metabolism. In this review, we provide an overview of metabolic reprogramming used by T cells, summarize the recent findings of key metabolic pathways and regulators modulating T cell homeostasis, differentiation, and function in the context of T1D, and discuss the opportunities for metabolic intervention to be employed to suppress autoreactive T cells and limit the progression of β-cell destruction.

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Section: Introductionmentioning

confidence: 99%

New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes

et al. 2022

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Role of Myokines and prospects for their role in Diabetes Mellitus Therapy

Nuriya,

Farida,

Sharma

et al. 2024

RJPT

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In the last decade, the attention of researchers has been drawn to the ability of skeletal muscles to produce biologically active substances (myokines). To date, several hundred myokines have been identified in the muscle secretome. Myokines have autocrine and paracrine effects. They have their own receptors in various tissues and organs. At certain concentrations, myokines have a systemic effect on tissues and organs, provide metabolic interaction between them and have a huge range of physiological effects. However, the biological activity of many of these myokines and their mechanism of action are either not yet characterized or poorly understood. Modern research is aimed at developing drugs that block myokine signaling pathways and studying the possibilities of their use in the treatment of neuromuscular diseases, obesity, type 2 diabetes mellitus, orthopedic pathology, as well as a decrease in muscle mass and muscle strength. Type 2 diabetes mellitus (T2DM) is a socially significant disease. Currently, there is no effective therapy to completely eradicate/cure diabetes and its associated complications. It is now necessary to consider in more detail the molecular pathways and targets for each pharmacological drug. There is a need to create new anti-diabetic therapy in the future based on myokines, knowing their signaling pathways and their mechanism of action on target cells, but also for the best possible combination therapy and strategies using available drugs and the beneficial effects of physical activity and exercise in the prevention and treatment of T2DM. A few studies in mice and humans have shown that exercise increases the levels of numerous myokines in the blood plasma, leading to the process of active transcription of myokines and accelerating metabolic processes associated with increased load on muscle tissue. It has been suggested that the secretion of myokines depends on the degree of physical training; intensity and duration of the athlete’s training; its physiological and anatomical structure; the sport in which the athlete plays. Further scientific research will provide the key to understanding the process of secretion of myokines (proteins) in the body and the mechanism of their effect on various organs/systems and tissues, which will undoubtedly contribute to the success of doctors in the field of practical healthcare in the correction of pathological disorders, including diabetes mellitus.

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Advanced Approaches in Immunotherapy for the Treatment of Type 1 Diabetes Mellitus

Cited by 2 publications

References 78 publications

New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes

New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes

Role of Myokines and prospects for their role in Diabetes Mellitus Therapy

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