Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes

Kong, Byung Soo; Min, Se Hee; Lee, Changhan; Cho, Young Min

doi:10.1016/j.celrep.2021.109447

Cited by 32 publications

(42 citation statements)

References 133 publications

(147 reference statements)

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“…Although no previous data has been reported about the association of intra-T cellular metabolism with beta-cell function progression, a few cross-sectional studies reported the status of T cell metabolism in T1D patients. Our results are similar to Kong BS’ research in 2021 which found that patients with T1D had enhanced CD4 + T cell glycolysis and decreased oxidative phosphorylation ( 40 ). Likewise, in NOD mice, increased 2NBDG uptake was also detected in NRP-V7-reactive T cells (a sort of diabetes pathogenic T cell) ( 21 ).…”

Section: Discussionsupporting

confidence: 92%

Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes

et al. 2022

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BackgroundAbnormal intracellular glucose/fatty acid metabolism of T cells has tremendous effects on their immuno-modulatory function, which is related to the pathogenesis of autoimmune diseases. However, the association between the status of intracellular metabolism of T cells and type 1 diabetes is unclear. This study aimed to investigate the uptake of glucose and fatty acids in T cells and its relationship with disease progression in type 1 diabetes.MethodsA total of 86 individuals with type 1 diabetes were recruited to detect the uptake of glucose and fatty acids in T cells. 2-NBDG uptake and expression of glucose transporter 1 (GLUT1); or BODIPY uptake and expression of carnitine palmitoyltransferase 1A(CPT1A) were used to assess the status of glucose or fatty acid uptake in T cells. Patients with type 1 diabetes were followed up every 3-6 months for 36 months, the progression of beta-cell function was assessed using generalized estimating equations, and survival analysis was performed to determine the status of beta-cell function preservation (defined as 2-hour postprandial C-peptide >200 pmol/L).ResultsPatients with type 1 diabetes demonstrated enhanced intracellular glucose uptake of T cells as indicated by higher 2NBDG uptake and GLUT1 expression, while no significant differences in fatty acid uptake were observed. The increased T cells glucose uptake is associated with lower C-peptide and higher hemoglobin A1c levels. Notably, patients with low T cell glucose uptake at onset maintained high levels of C-peptide within 36 months of the disease course [fasting C-petite and 2-hour postprandial C-peptide are 60.6 (95%CI: 21.1-99.8) pmol/L and 146.3 (95%CI: 14.1-278.5) pmol/L higher respectively], And they also have a higher proportion of beta-cell function preservation during this follow-up period (P<0.001).ConclusionsIntracellular glucose uptake of T cells is abnormally enhanced in type 1 diabetes and is associated with beta-cell function and its progression.

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Section: Discussionsupporting

confidence: 92%

Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes

et al. 2022

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“…Second, our results showed a clear increase in MOTS-c in obese mothers' blood in comparison to healthy control women. This observation confirms that MOTS-c is an important factor regulating metabolism, possibly also as a factor in preventing damage to pancreatic islets [29]. An increase in the level of MOTS-c implies that the organism attempts to maintain high glucose utilization and limit the growth of adipose tissue.…”

Section: Discussionsupporting

confidence: 72%

Changes in MOTS-c Level in the Blood of Pregnant Women with Metabolic Disorders

Wojciechowska

Pruszyńska‐Oszmałek

Kołodziejski

et al. 2021

Biology

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MOTS-c peptide is a member of the group of mitochondria-derived peptides (MDP). It is a product of the open reading frame in the 12S RNA gene. Due to its features and functions in the body, this peptide is classified as a hormone. The first publications indicated that this hormone improves insulin sensitivity and lowers body weight in obese animals. This suggests that it may be an important peptide in maintaining the body's energy homeostasis. The aim of our work was to investigate the potential role of MOTS-c peptide during pregnancy, which is a condition prone to metabolic disorders. The research covered healthy, obese women and women with thyroid disorders. The obtained results indicated an increase in the concentration of MOTS-c in the blood of mothers and newborns in the obese group as compared to the healthy control group and a corresponding decrease in the concentration of this peptide in mothers and newborns in the group with hypothyroidism compared to the obese group. Moreover, we also observed a strong positive correlation between the concentration of MOTS-c in maternal blood and in umbilical cord blood. In summary, the MOTS-c peptide shows changes in blood concentration in various physiological states and may, in the future, become an important tool in the fight against metabolic diseases such as obesity or type 2 diabetes.

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“…For example, αCD3/αCD28 increased ECAR level from the basal level of 2 mpH/min to 4 mpH/min. However, ECAR level of MOTS-c treated T cells had subtle changes of ECAR after αCD3/αCD28 in our previous work ( Kong et al., 2021 ). MOTS-c treatment can cause a variety of metabolic changes in different cell types Ahn et al, 2020 , Lee et al, 2015 .…”

Section: Expected Outcomesmentioning

confidence: 58%

“…This protocol is useful to analyze different subsets of T cells and applicable to different autoimmune disease models (i.e., T1D, multiple sclerosis). For complete details on the use and execution of this profile, please refer to Kong et al. (2021) .…”

mentioning

confidence: 99%

Protocol for the assessment of human T cell activation by real-time metabolic flux analysis

2022

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Summary The elevation of glycolysis in autoreactive T cells is a key target for the prevention and treatment of T cell-related autoimmune diseases, such as type 1 diabetes (T1D). Here, we describe a simple and efficient protocol for isolating human peripheral blood mononuclear cells (PBMCs) and T cells, and the subsequent assessment of T cell glycolysis using Seahorse analyzer. This protocol is useful to analyze different subsets of T cells and applicable to different autoimmune disease models (i.e., T1D, multiple sclerosis). For complete details on the use and execution of this profile, please refer to Kong et al. (2021) .

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Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes

Cited by 32 publications

References 133 publications

Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes

Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes

Changes in MOTS-c Level in the Blood of Pregnant Women with Metabolic Disorders

Protocol for the assessment of human T cell activation by real-time metabolic flux analysis

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