GDF15: a potential therapeutic target for type 1 diabetes

Sarkar, Soumyadeep; Melchior, John T.; Henry, Hayden R.; Syed, Farooq; Mirmira, Raghavendra G.; Nakayasu, Ernesto S.; Metz, Thomas O.

doi:10.1080/14728222.2022.2029410

GDF15: a potential therapeutic target for type 1 diabetes

Journal Article · Tue Feb 08 23:00:00 EST 2022 · Expert Opinion on Therapeutic Targets

DOI:https://doi.org/10.1080/14728222.2022.2029410· OSTI ID:1855997

^[1]; ^[2]; Henry, Hayden R. ^[1]; ^[3]; ^[4]; ^[1]; ^[1]

Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Univ. of Cincinnati, OH (United States)
Indiana University School of Medicine, Indianapolis, IN United States)
Univ. of Chicago, IL (United States)

Type 1 Diabetes (T1D) is a pancreatic disease, which is marked by immune-mediated ? cell destruction causing hyperglycemic phenotype. Recently, our team has demonstrated the beneficial role of GDF15 in preventing T1D-associated insulitis. Therefore, in this review, we discuss the therapeutic potential of GDF15 in treating T1D and map the promising avenues demanding increased focus in this field. Areas covered: Several therapeutic options exist for management of T1D, however, the demand for new and efficient therapies persists, particularly for interventions that may prevent or delay disease onset. Growth differentiation factor 15 (GDF15) is a known diabetes biomarker which has shown impressive tissue-protective actions across a broad range of metabolic disorders. There is a tremendous amount of overlap between the two topics (GDF15 & T1D), however, the connections were uncharted. We discuss all these connections and the possibility of exploiting them to make GDF15 a T1D therapy. Expert Opinion: The newly discovered GDF15 primary receptor and associated signaling pathway has accelerated the excitement by making it a druggable target. However, the there exists a huge gap in knowledge regarding the mechanism by which GDF15 functions in the peripheral tissues. In this context, reports of GDF15 receptor in pancreas, gives a convincing argument of direct GDF15 effect. Further, GDF15’s role in regulating mitochondrial, ER and metabolic stress, makes it an ideal T1D candidate.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1855997

Report Number(s):: PNNL-SA-168207

Journal Information:: Expert Opinion on Therapeutic Targets, Journal Name: Expert Opinion on Therapeutic Targets Journal Issue: 1 Vol. 26; ISSN 1472-8222

Publisher:: Taylor & FrancisCopyright Statement

Country of Publication:: United States

Language:: English

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Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet Dostálová, Ivana; Roubíček, Tomáš; Bártlová, Markéta European Journal of Endocrinology, Vol. 161, Issue 3 https://doi.org/10.1530/EJE-09-0417	journal	September 2009
Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study Carstensen, Maren; Herder, Christian; Brunner, Eric J. European Journal of Endocrinology, Vol. 162, Issue 5 https://doi.org/10.1530/EJE-09-1066	journal	May 2010
Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial Kempf, Tibor; Guba-Quint, Anja; Torgerson, Jarl European Journal of Endocrinology, Vol. 167, Issue 5 https://doi.org/10.1530/EJE-12-0466	journal	November 2012
The circadian clock regulates cisplatin-induced toxicity and tumor regression in melanoma mouse and human models Dakup, Panshak P.; Porter, Kenneth I.; Little, Alexander A. Oncotarget, Vol. 9, Issue 18 https://doi.org/10.18632/oncotarget.24539	journal	February 2018
GDF15 promotes EMT and metastasis in colorectal cancer Li, Chen; Wang, Jingyu; Kong, Jianlu Oncotarget, Vol. 7, Issue 1 https://doi.org/10.18632/oncotarget.6205	journal	October 2015
Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms Nguyen, Cao; Varney, Michael D.; Harrison, Leonard C. Diabetes, Vol. 62, Issue 6 https://doi.org/10.2337/db12-1398	journal	May 2013
The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud Diabetes, Vol. 65, Issue 9 https://doi.org/10.2337/db15-0629	journal	April 2016
Growth Differentiation Factor 15 Mediates Systemic Glucose Regulatory Action of T-Helper Type 2 Cytokines Lee, Seong Eun; Kang, Seul Gi; Choi, Min Jeong Diabetes, Vol. 66, Issue 11 https://doi.org/10.2337/db17-0333	journal	September 2017
The Rising Incidence of Type 1 Diabetes Is Accounted for by Cases With Lower-Risk Human Leukocyte Antigen Genotypes Fourlanos, Spiros; Varney, Michael D.; Tait, Brian D. Diabetes Care, Vol. 31, Issue 8 https://doi.org/10.2337/dc08-0239	journal	August 2008
Plasma Growth Differentiation Factor-15 Independently Predicts All-Cause and Cardiovascular Mortality As Well As Deterioration of Kidney Function in Type 1 Diabetic Patients With Nephropathy Lajer, Maria; Jorsal, Anders; Tarnow, Lise Diabetes Care, Vol. 33, Issue 7 https://doi.org/10.2337/dc09-2174	journal	March 2010
The TGF-β superfamily cytokine, MIC-1/GDF15: A pleotrophic cytokine with roles in inflammation, cancer and metabolism Breit, Samuel N.; Johnen, Heiko; Cook, Andrew D. Growth Factors, Vol. 29, Issue 5 https://doi.org/10.3109/08977194.2011.607137	journal	August 2011
GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin Ouyang, Jing; Isnard, Stéphane; Lin, John Frontiers in Endocrinology, Vol. 11 https://doi.org/10.3389/fendo.2020.581839	journal	November 2020
The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes Niu, Yixin; Zhang, Weiwei; Shi, Jie Frontiers in Endocrinology, Vol. 12 https://doi.org/10.3389/fendo.2021.627395	journal	March 2021
Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint Wischhusen, Jörg; Melero, Ignacio; Fridman, Wolf Herman Frontiers in Immunology, Vol. 11 https://doi.org/10.3389/fimmu.2020.00951	journal	May 2020
A Novel Small Molecule GDNF Receptor RET Agonist, BT13, Promotes Neurite Growth from Sensory Neurons in Vitro and Attenuates Experimental Neuropathy in the Rat Sidorova, Yulia A. Frontiers in Pharmacology, Vol. 8 https://doi.org/10.3389/fphar.2017.00365	journal	January 2017
Increased Growth Differentiation Factor 15 in Patients with Hypoleptinemia-Associated Lipodystrophy Kralisch, Susan; Hoffmann, Annett; Estrada-Kunz, Juliane International Journal of Molecular Sciences, Vol. 21, Issue 19 https://doi.org/10.3390/ijms21197214	journal	September 2020
Effect of Weight Loss by Low-Calorie Diet on Cardiovascular Health in Type 2 Diabetes: An Interventional Cohort Study Melhem, Shaden; Steven, Sarah; Taylor, Roy Nutrients, Vol. 13, Issue 5 https://doi.org/10.3390/nu13051465	journal	April 2021
NSAID Activated Gene (NAG-1), a Modulator of Tumorigenesis Eling, Thomas E.; Baek, Seung-Joon; Shim, Min-sub BMB Reports, Vol. 39, Issue 6 https://doi.org/10.5483/BMBRep.2006.39.6.649	journal	November 2006
Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI Tsai, Vicky figshare https://doi.org/10.6084/m9.figshare.1443589.v1	dataset	January 2015

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59 BASIC BIOLOGICAL SCIENCES
ER stress
GDF15
Type 1 diabetes (T1D)
Type 2 diabetes (T2D)
chronotherapy
immunomodulator
insulitis
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GDF15: a potential therapeutic target for type 1 diabetes Sarkar, Soumyadeep; Melchior, John T.; Henry, Hayden R. https://doi.org/10.6084/m9.figshare.19146484 The current record is supplemented by this dataset	dataset	January 2022
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GDF15: a potential therapeutic target for type 1 diabetes

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