Basal and T3-induced ROS Production in Lymphocyte Mitochondria is Increased in Type 2 Diabetic Patients

Anthonsen, Stine; Larsen, Jacob; Pedersen, Palle; Dalgaard, Louise Torp; Kvetny, Jan

doi:10.1055/s-0032-1327590

Cited by 4 publications

(5 citation statements)

References 23 publications

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“…In euthyroid humans, serum T 3 is predominantly generated by outer-ring deiodination of T 4 to T 3 by type 2 deiodinase (D2) [17]. We have previously demonstrated how in vitro T 3 and T 2 stimulation is able to increase the MMP [18] and mitochondrial ROS production in PBMCs [7], while others reported thyroid hormone-induced increases in ROS production in PBMCs in vivo [19]. Although the T 4 /T 3 ratio did not change after hemithyroidectomy, mitochondrial hyperpolarization might be a result of an increased conversion of T 4 to T 3 by D2 and subsequently to T 2 , known to stimulate mitochondria directly [18], as decreased levels of serum T 4 /T 3 in rodent models of hypothyroidism increase D2 activity in white adipose tissue [20] and skeletal muscle [21].…”

Section: Discussionmentioning

confidence: 99%

“…The resuspended cells were incubated for 30 min at room temperature in the dark. After incubation, the test tubes were chilled on ice until the fluorescence intensity of the stained PBMCs was measured by flow cytometry (BD Accuri™ C6 Flow Cytometer) according to a previously described method [7]. MTG fluorescence was recorded in the FL1 (FITC) channel and TMRM fluorescence in the FL2 (PE) channel.…”

Section: Methodsmentioning

confidence: 99%

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Persistent Cellular Metabolic Changes after Hemithyroidectomy for Benign Euthyroid Goiter

Kristensen¹,

Larsen²,

Pedersen³

et al. 2014

Eur Thyroid J

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Background: The significance of perturbations of thyroid-stimulating hormone (TSH) and thyroid hormones within the laboratory reference ranges after hemithyroidectomy is unknown. Our aim was to examine changes in TSH and thyroid hormones after hemithyroidectomy for benign euthyroid goiter, focusing on tissue response by examining the mitochondrial membrane potential (MMP) of peripheral blood mononuclear cells (PBMCs) and basal oxygen consumption (V˙O₂). Materials and Methods: In a prospective study on 28 patients and controls, we examined serum TSH and thyroid hormones before hemithyroidectomy and 1, 3, 6 and 12 months after hemithyroidectomy for benign euthyroid goiter. In the hemithyroidectomy group, flow cytometry was used to measure the MMP of tetramethylrhodamine methyl ester (TMRM)- and MitoTracker Green (MTG)-stained PBMCs, and V˙O₂ was measured by an Oxycon Pro apparatus. Results: One year after hemithyroidectomy, TSH had increased from a median of 0.97 mIU/l (interquartile range, IQR: 0.69-1.50 mIU/l) to 2.10 mIU/l (IQR: 1.90-3.00 mIU/l; p < 0.001); free thyroxine (fT₄) had decreased from a median of 16.0 pmol/l (IQR: 14.9-17.0 pmol/l) to 14.8 pmol/l (IQR: 14.1-16.4 pmol/l; p = 0.009), whereas total triiodothyronine variations did not differ from those in controls. Concomitantly, the MMP of TMRM- and MTG-stained PBMCs was increased by 58% (p < 0.001) and 22% (p = 0.008), respectively. V˙O₂ was increased by 14% (p = 0.01). Conclusion: Hemithyroidectomy for benign euthyroid goiter induced persistently increased TSH and decreased fT₄, sustained mitochondrial hyperpolarization and increased V˙O₂. Our results demonstrate a decrease after hemithyroidectomy of the metabolic state to which the individual is adapted, with persistent cellular metabolic changes in a hemithyroidectomized patient group which is normally considered clinically and biochemically euthyroid.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Persistent Cellular Metabolic Changes after Hemithyroidectomy for Benign Euthyroid Goiter

Kristensen¹,

Larsen²,

Pedersen³

et al. 2014

Eur Thyroid J

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“…Interestingly, basal ROS concentration was increased in lymphocytes from type 2 DM and triiodothyronine (T 3 ) significantly stimulated ROS concentration in type 2 DM patients. Thus an increased mitochondrial sensitivity for T3 may be a significant factor responsible for increased ROS production in diabetic patients [ 103 ].…”

Section: Role Of Mitochondrial Dysfunction In Diabetic Lung Injurymentioning

confidence: 99%

Potential Biochemical Mechanisms of Lung Injury in Diabetes

Zheng¹,

Wu²,

Jin³

et al. 2017

Aging and disease

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Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury.

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“…According to previous reports, low-grade and sub-clinical inflammation and pain depend on the risk factors for diabetes and insulin resistance in hyperglycemia ( Figure 3 ) ( Hey-Mogensen et al, 2010 ; Anthonsen, Larsen, Pedersen, Dalgaard, & Kvetny, 2013 ; Kassan et al, 2014 ; Manoharan et al, 2019 ). The reactive oxygen species (ROS) generation signals for neuropathy associated with DM complications (J. P. Chen, Xu, Liao, & Zhang, 2020 ; S. H. Lee et al, 2016 ; Nogueira-Machado et al, 2006 ; Sommese et al, 2018 ).…”

Section: Oxidative Stress Mechanistic Features In Diabetic Neuropathymentioning

confidence: 62%

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

et al. 2022

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Pre-diabetes and diabetes are growing threats to the modern world. Diabetes mellitus (DM) is associated with comorbidities such as hypertension (83.40%), obesity (90.49%), and dyslipidemia (93.43%), creating a substantial burden on patients and society. Reductive and oxidative (Redox) stress level imbalance and inflammation play an important role in DM progression. Various therapeutics have been investigated to treat these neuronal complications. Melatonin and dipeptidyl peptidase IV inhibitors (DPP-4i) are known to possess powerful antioxidant and anti-inflammatory properties and have garnered significant attention in the recent years. In this present review article, we have reviewed the recently published reports on the therapeutic efficiency of melatonin and DPP-4i in the treatment of DM. We summarized the efficacy of melatonin and DPP-4i in DM and associated complications of diabetic neuropathy (DNP) and neuropathic pain. Furthermore, we discussed the mechanisms of action and their efficacy in the alleviation of oxidative stress in DM.

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Basal and T3-induced ROS Production in Lymphocyte Mitochondria is Increased in Type 2 Diabetic Patients

Cited by 4 publications

References 23 publications

Persistent Cellular Metabolic Changes after Hemithyroidectomy for Benign Euthyroid Goiter

Persistent Cellular Metabolic Changes after Hemithyroidectomy for Benign Euthyroid Goiter

Potential Biochemical Mechanisms of Lung Injury in Diabetes

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

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