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Organ Cross-Talk Regulates (Brain) Insulin Action
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Besides IGF1 and FGF21, there are other beneficial hepatokines that improve glucose homeostasis, such as activin-E, ANGPTL6, GDF15, lipocalin 13, and SMOC1. They are not further discussed here but can be studied in a review (166).
Stroke and Transient Ischemic Attacks of the Brain and Eye
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
The risk of bleeding with anticoagulation increases with higher HAS-BLED and ABC bleeding scores (age, biomarkers [hemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI] and clinical history of previous bleeding]). Although the presence of CMBs on MRI are associated with a greater relative hazard (adjusted HR) for subsequent ICH than for ischemic stroke (e.g. for >5 CMBs, the aHR is 4.55 [95% CI: 3.08–6.72] for ICH vs. 1.47 [1.19–1.80] for ischemic stroke), the absolute risk of ischemic stroke is higher than that of ICH, regardless of CMB presence, anatomical distribution, or burden.88
Mitochondrial Pathologies and Their Neuromuscular Manifestations
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Carlos Ortez, Andrés Nascimento
Proximal weakness and hypotonia appear mainly between birth and 24 months and evolve into respiratory failure, the main cause of death. Other features include facial diplegia, PEO, exercise intolerance, and severe feeding difficulties. The marked increase of CK in serum, unusual in mitochondrial myopathies, is a useful diagnostic clue. Most patients have lactic acidosis, a myopathic pattern on EMG, numerous RRF and COX fibers on muscle biopsy and generalized deficiency of RC with reduction of mtDNA copy number. Recently our group has identified a new mitochondrial biomarker, the growth and differentiation factor-15 (GDF15) useful to identify patients with TK2 mutations in witch not significant increased of CK or serum lactate were observed31,32.
MT1-MMP – A potential drug target for the management of the obesity
Published in Expert Opinion on Therapeutic Targets, 2022
Pallavi Asthana, Xuanming Guo, Hoi Leong Xavier Wong
It is well known that endogenous level of GDF15 is remarkably elevated during obesity and related metabolic complications. A fold change of up to 10-fold, with serum levels in the range of ~0.02–0.1 ng/ml in lean versus ~0.15–0.6 ng/ml in obese mice has been reported [11]. This suggests that obesity may be a state of resistance for endogenous GDF15 at least in the physiological condition. Our findings indeed showed a potential mechanism driven by MT1-MMP underlying the obesity-associated resistance for endogenous GDF15. The expression of MT1-MMP may determine the threshold of circulating GDF15 required to induce positive effects on metabolism in the context of obesity. Our study thus identified the physiological setting in which MT1-MMP plays the role in relation to the phenomenon of GDF15 resistance, an emerging research area with important clinical implications. In addition to GDF15/GFRAL signaling axis, MT1-MMP has been shown to regulate diverse intracellular signaling pathways associated with energy metabolism, including fibroblast growth factor (FGF)/FGFRs signaling [12–15]. Further investigations will be required to further delineate the molecular mechanism underlying MT1-MMP-dependent regulation of energy homeostasis.
GDF15: a potential therapeutic target for type 1 diabetes
Published in Expert Opinion on Therapeutic Targets, 2022
Soumyadeep Sarkar, John T. Melchior, Hayden R. Henry, Farooq Syed, Raghavendra G. Mirmira, Ernesto S. Nakayasu, Thomas O. Metz
While GDF15 is best recognized for its influence on metabolism, it acts in several homeostatic mechanisms in the body. Multiple studies have now shown that GDF15 plays a critical anti-inflammatory role in tissue injury. Most of our mechanistic insights on the role of GDF15 in inflammation come from an early study by Kempf and colleagues, who reported that GDF15 inhibits integrin activation and thereby dampens cytokine signaling and infiltration of pro-inflammatory cells in heart infarcts [35]. In addition, Abulizi et al. and Santos et al. demonstrated that GDF15 deficiency exacerbates the inflammatory response to sepsis affected tissue, but its role is highly contextual [36,37]. Similarly, in animal models of T1D, Deelman and colleagues showed that GDF15 deficiency results in increased expression of inflammatory markers [38]. In contrast, Santos et al. showed that GDF15’s immunomodulatory role has also been demonstrated in tumorigenesis and cancer progression with contradictory viewpoints, making it difficult to clearly define its underlying mechanism of action as an anti-inflammatory molecule [39–41]. However, the above studies indicate a tissue-protective role of GDF15 in addition to the parasympathetic signaling axis.
Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension
Published in Biomarkers, 2020
Steffen D. Kriechbaum, Christoph B. Wiedenroth, Karina Peters, Marta A. Barde, Ruth Ajnwojner, Jan-Sebastian Wolter, Moritz Haas, Fritz C. Roller, Stefan Guth, Andreas J. Rieth, Andreas Rolf, Christian W. Hamm, Eckhard Mayer, Till Keller, Christoph Liebetrau
GDF-15, a member of the transforming growth factor-β superfamily, is expressed at a low level in almost all types of tissue (Mueller et al.2015) and is upregulated in response to different kinds of tissue injury resulting from inflammation, shear stress, or ischaemia that occur in various diseases (Nickel et al.2011, Mueller et al.2015). A wide range of GDF-15 levels have been reported in healthy and diseased individuals (Wollert et al.2017). Median values between 600 and 1500 pg/ml, with an upper limit of normal of 1200 ng/L (patients >50 years), were reported in population studies (Wollert et al.2017) , and for patients with stable coronary artery disease, acute myocardial ischaemia, or heart failure levels ranging from 1200 to 3600 pg/ml have been cited (Wollert et al.2017). In a mixed PH cohort the values ranged from 400 to 1495 pg/ml, with the few CTEPH patients included mostly showing values in the lower tertile (Geenen 2020). Two further studies reported median GDF-15 levels of 1580 pg/ml (n = 82) (Klok et al.2011) and 1306 pg/ml (n = 12) (Mirna et al.2020) in CTEPH patients. In our study, CTEPH patients had higher GDF-15 levels (median of 820 [556–1315] pg/ml) than healthy controls.