Thyroid hormones in diabetes, cancer, and aging

Gauthier, Benoît; Sola-García, Alejandro; Cáliz-Molina, María Ángeles; Lorenzo, Petra I.; Cobo-Vuilleumier, Nadia; Capilla-González, Vivian; Martín-Montalvo, Aléjandro

doi:10.1111/acel.13260

Cited by 90 publications

(59 citation statements)

References 280 publications

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“…On the other hand, although tafamidis does not seem to exhibit any other activity analog to hormonal molecules, thyromimetics have attracted attention for their therapeutic TH-like effects [ 29 , 30 , 31 , 32 ]. Diverse thyromimetics have been developed to modulate their activity, permeability, and selectivity, without hampering their therapeutic benefits [ 31 , 33 ]. In particular, a series of thyromimetics specific for TH receptor β (TRβ) demonstrated various advantageous features against neurodegenerative diseases and metabolic disorders, without the severe side effects often mediated by the activation of TH receptor α [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Runfola

Rapposelli

et al. 2021

IJMS

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Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Runfola

Rapposelli

et al. 2021

IJMS

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“…The interest for the TH–cancer association was rekindled with the cloning of cDNAs encoding the nuclear TH receptors (TRs) in 1986 [ 5 ], which heralded a new realm of investigation. In 1993, the case report of spontaneous remission of metastatic NSCLC following recovery from myxedema coma by Hercbergs and Leith [ 6 ] paved the way for the increasing recognition of the implication of TH in a wide array of malignancies beyond the lung, including breast, prostate, ovary, adrenocortical, thyroid, colon, hepatocellular, and pancreatic cancer and melanoma, glioma, glioblastoma, multiple myeloma, lymphoma, sarcoma, and leukemia [ 4 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Deligiorgi

Trafalis

2021

IJMS

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Exemplifying the long-pursued thyroid hormones (TH)–cancer association, the TH–lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH–lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting. TH contribute to all hallmarks of cancer through integration of diverse actions, currently classified according to molecular background. Despite the increasingly recognized implication of TH in lung cancer, three pending queries need to be resolved to empower a tailored approach: (1) How to stratify patients with TH-sensitive lung tumors? (2) How is determined whether TH promote or inhibit lung cancer progression? (3) How to mimic the antitumor and/or abrogate the tumor-promoting TH actions in lung cancer? To address these queries, research should prioritize the elucidation of the crosstalk between TH signaling and oncogenic signaling implicated in lung cancer initiation and progression, and the development of efficient, safe, and feasible strategies leveraging this crosstalk in therapeutics.

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“…A possible mechanism for this is their respective roles in the synthesis of thyroid hormones. Thyroid hormones are efficient modulators of catabolism of energy sources (including carbohydrates) and both hyperthyroidism and hypothyroidism have been associated with the development of diabetes [105]. A positive relationship has been observed between thyroid stimulating hormone and HOMA-IR, indicating hypothyroidism has a role in insulin resistance and diabetes [106,107].…”

Section: Iodine and Selenium Intakes And Glucose Metabolismmentioning

confidence: 99%

Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis

Norbitt

Kimita

et al. 2021

Nutrients

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Associations between habitual dietary intake of minerals and glucose metabolism have been extensively studied in relation to metabolic disorders. However, similar research has yet to be conducted in individuals after acute pancreatitis (AP). The main aim was to investigate the associations between habitual intake of 13 minerals and glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Associations between the dietary intake of minerals and markers of glucose metabolism (glycated haemoglobin and fasting plasma glucose) were also studied. The EPIC-Norfolk food frequency questionnaire was used in a cross-sectional fashion to determine the habitual intake of 13 dietary minerals. ANCOVA as well as multiple linear regression analyses were conducted and five statistical models were built to adjust for covariates. The study included 106 individuals after AP. In the NODAP group, intake of 4 minerals was significantly less when compared with the NAP group: iron (B = −0.076, p = 0.013), nitrogen (B = −0.066, p = 0.003), phosphorous (B = −0.046, p = 0.006), and zinc (B = −0.078, p = 0.001). Glycated haemoglobin was significantly associated with iodine intake (B = 17.763, p = 0.032) and manganese intake (B = −17.147, p = 0.003) in the NODAP group. Fasting plasma glucose was significantly associated with manganese intake (B = −2.436, p = 0.027) in the NODAP group. Habitual intake of minerals differs between individuals with NODAP, T2DM, and NAP. Prospective longitudinal studies and randomised controlled trials are now warranted to further investigate the associations between mineral intake and NODAP.

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Thyroid hormones in diabetes, cancer, and aging

Cited by 90 publications

References 280 publications

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis

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