Review
Endocrinology & Metabolism
Harleen Kaur, Beverly S. Muhlhausler, Claire T. Roberts, Kathryn L. Gatford
Summary: The growth hormone (GH)-insulin-like growth factor (IGF) axis undergoes significant changes during pregnancy, with increased secretion of GH and IGFs leading to maternal metabolic adaptations, enhanced placental function, and fetal growth. Exogenous GH or IGF treatment in animal models of normal and compromised pregnancy also promotes similar effects, suggesting alternative approaches to enhance maternal GH abundance during pregnancy for better maternal and fetal outcomes.
JOURNAL OF ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mariam Ahmed Galal, Samhar Samer Alouch, Buthainah Saad Alsultan, Huda Dahman, Nouf Abdullah Alyabis, Sarah Ammar Alammar, Ahmad Aljada
Summary: This comprehensive review thoroughly explores the intricate involvement of insulin receptor isoforms and insulin-like growth factor receptors in the insulin and insulin-like growth factor signaling pathway, emphasizing their crucial roles in cancer development and resistance to anti-cancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Baylea N. Davenport, Helen N. Jones, Rebecca L. Wilson
Summary: Clinically, fetal growth restriction (FGR) is only detectable in later gestation, despite pathophysiological establishment likely earlier in pregnancy. Additionally, there are no effective in utero treatment options for FGR. We have developed a nanoparticle to deliver human insulin-like 1 growth factor (hIGF-1) in a trophoblast-specific manner which results in increased expression of hIGF-1. IGF-1 signaling in the placenta regulates multiple developmental processes including trophoblast invasion and maternal vascular remodeling, both of which can be diminished in the FGR placenta. We aimed to determine the effects of short-term hIGF-1 nanoparticle treatment on sub-placenta/decidua trophoblast signaling mechanisms in FGR and under normal growth conditions.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Endocrinology & Metabolism
Derek LeRoith, Jeff M. P. Holly, Briony E. Forbes
Summary: The IGF family of ligands, receptors, and binding proteins play critical roles in normal human physiology and disease states. IGF-I regulates cellular growth, differentiation, and survival to control overall body growth, while IGF-II has important effects prenatally and in tissue-specific roles in adults.
MOLECULAR METABOLISM
(2021)
Article
Oncology
Seyda Berk, Joseph A. M. J. L. Janssen, Peter M. van Koetsveld, Fadime Dogan, Naci Degerli, Servet Ozcan, Fahrettin Kelestimur, Leo J. Hofland
Summary: The effects of glucose, insulin, and IGF on the growth of colon cancer cells vary between early and late stages. Glucose plays a more significant role in stimulating proliferation in early stage cells, while growth factor-mediated stimulation becomes more pronounced in late stage cells. Strict glucose control may be crucial in controlling tumor growth in early stages, while inhibiting the endocrine actions of IGFs and insulin is more important in late stages of colorectal cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biology
Ji-Sun Lee, Claire E. Tocheny, Leslie M. Shaw
Summary: This review provides an overview of the role of the IGF signaling pathway in breast cancer and discusses its potential as a therapeutic target. Dysregulation of IGF pathway components contributes to breast cancer risk and progression, and the pathway has also been implicated in resistance to current therapies. Unfortunately, targeting IGF signaling for breast cancer treatment has been unsuccessful so far due to adverse effects on normal glucose metabolism. However, recent discoveries offer hope for continued efforts in this area.
Review
Endocrinology & Metabolism
Mengyang Li
Summary: The GH/IGF system plays a role in growth regulation in the body. By studying the basal chordate amphioxus, it was discovered that most members of the GH/IGF system are present in amphioxus, providing strong evidence for the origin of this system in amphioxus.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Julian Bailes, Mikhail Soloviev
Summary: IGF-1, the principal mediator of GH, plays a crucial role in cell growth, differentiation, and apoptosis, with its bioavailability affected by IGFBPs. The varying expression levels of IGF-1 in clinical conditions and its misuse in sports have raised significant concerns.
Article
Endocrinology & Metabolism
Mirela-Diana Ilie, Antoine Tabarin, Alexandre Vasiljevic, Jean-Francois Bonneville, Lucile Moreau-Grange, Franck Schillo, Brigitte Delemer, Anne Barlier, Dominique Figarella-Branger, Segolene Bisot-Locard, Alexandre Santos, Philippe Chanson, Gerald Raverot
Summary: This study aimed to explore the factors related to SRLs in the treatment of acromegaly and confirmed that SST2A and adenoma granularity are good predictors of response to octreotide. In addition, the optimization of MRI sequences is important for using T2WSI as a predictor of treatment response.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Biochemistry & Molecular Biology
Tomoko Okuyama, Mayu Kyohara, Yasuo Terauchi, Jun Shirakawa
Summary: IGFs mainly mediate long-term actions in cell fates, while insulin predominantly exerts its role on metabolic activities. The interactions between insulin receptor signaling and IGF-I receptor signaling in metabolism and cell fates are complicated, and the function of IGF-I in respective tissues remains insufficiently understood. Clarifying the precise roles of IGF-I signaling on metabolism separate from those of insulin signaling is necessary.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Jingran Cao, Douglas Yee
Summary: The IGF system plays a crucial role in regulating malignancies, but blocking this system has not shown significant benefits in clinical trials. Targeting Type I IGF receptor alone may not be sufficient to disrupt this pathway, as the insulin receptor may also play a relevant role as a cancer target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Leonie Rieger, Rosemary O'Connor
Summary: The internalization and localization of the IGF-1 receptor play crucial roles in cell signaling and biological processes, with different cell types and cell adhesion receptors regulating this process. Further study on how IGF-1R intracellular trafficking and compartmentalized signaling is controlled, particularly in cancer, is needed.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
S. Chandhini, Bushra Trumboo, Seena Jose, Tincy Varghese, M. Rajesh, V. J. Rejish Kumar
Summary: The insulin-like growth factor signalling system plays a crucial role in the growth and development of fishes and shellfishes, serving as important biomarkers for assessing growth and nutritional status in aquaculture.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Obstetrics & Gynecology
Elena N. Alekseenkova, V. N. Babakov, S. A. Selkov, G. C. Di Renzo, I. Yu. Kogan, R. V. Kapustin
Summary: This study investigated the relationship between maternal insulin-like growth factor (IGF) levels and fetal macrosomia. The authors found that higher levels of first-trimester IGF-1 and a higher IGF-1/IGFBP-1 ratio were associated with large-for-gestational-age neonates. The IGF-1/IGFBP-1 ratio showed better performance in predicting birth weight over 4000 g.
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
(2023)
Review
Endocrinology & Metabolism
Haim Werner, Zvi Laron
Summary: The GH-IGF1 signaling pathway plays a key role in aging and longevity. Patients with LS, a congenital IGF1 deficiency, seem to be protected from cancer. Aging and cancer may be different manifestations of the same underlying processes. Genome-wide screenings have identified genes associated with aging and longevity in LS patients.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Transplantation
Laust Dupont Rasmussen, Morten Bottcher, Per Ivarsen, Hanne Skou Jorgensen, Mette Nyegaard, Henriette Buttenschon, Camilla Gustafsen, Simon Glerup, Hans Erik Botker, My Svensson, Simon Winther
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2020)
Article
Pharmacology & Pharmacy
Ditte Olsen, Mathias Kaas, Jesper Lundhede, Simon Molgaard, Anders Nykjaer, Mads Kjolby, Soren D. Ostergaard, Simon Glerup
FRONTIERS IN PHARMACOLOGY
(2019)
Letter
Physiology
Gitte R. Hinrichs, Kathrin Weyer, Ulla G. Friis, Per Svenningsen, Ida Katrine Lund, Rikke Nielsen, Geraldine Mollet, Corinne Antignac, Claus Bistrup, Boye L. Jensen, Henrik Birn
Article
Neurosciences
Abdel-Rahman Al-Absi, Per Qvist, Samora Okujeni, Ahmad Raza Khan, Simon Glerup, Connie Sanchez, Jens R. Nyengaard
MOLECULAR NEUROBIOLOGY
(2020)
Article
Psychiatry
Ditte Olsen, Niels Wellner, Mathias Kaas, Inge E. M. de Jong, Florence Sotty, Michael Didriksen, Simon Glerup, Anders Nykjaer
Summary: Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder worldwide, and Sorcs2(-/-) mice can replicate symptoms reminiscent of ADHD. Research shows that loss of the SorCS2 gene affects dopaminergic circuit function and behavioral responses to the environment.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Cell Biology
Katerina O. Gospodinova, Ditte Olsen, Mathias Kaas, Susan M. Anderson, Jonathan Phillips, Rosie M. Walker, Mairead L. Bermingham, Abigail L. Payne, Panagiotis Giannopoulos, Divya Pandya, Tara L. Spires-Jones, Catherine M. Abbott, David J. Porteous, Simon Glerup, Kathryn L. Evans
Summary: This study reveals a novel role for SORCS2 in DNA double-strand break formation, showing that loss of SORCS2 leads to increased DSB levels and reduced neuronal viability. These findings contribute to our understanding of the pathogenesis of neurodegenerative disorders.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Maj Ulrichsen, Nadia P. Goncalves, Simin Mohseni, Simone Hjaeresen, Thomas L. Lisle, Simon Molgaard, Niels K. Madsen, Olav M. Andersen, Asa F. Svenningsen, Simon Glerup, Anders Nykjaer, Christian B. Vaegter
Summary: This study demonstrates the importance of sortilin in the formation of Remak bundles after sciatic nerve injury. Loss of sortilin does not affect the morphology and conduction velocity of myelinated fibers, but results in abnormal ensheathment of injured C-fibers. Furthermore, the study shows that sortilin deletion leads to a significant reduction in MAPK/ERK, RSK, and CREB phosphorylation in Schwann cells stimulated with neurotrophin-3 (NT-3).
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Abdel-Rahman Al-Absi, Sakeerthi Kethees Thambiappa, Ahmad Raza Khan, Simon Glerup, Connie Sanchez, Anne M. Landau, Jens R. Nyengaard
Summary: The hemizygous deletion in the 22q11.2 locus leads to dysregulations in inhibitory circuits, involving reduced binding levels of GABAA receptors, as well as functional and structural modulations of the excitatory networks in the hippocampus.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Immunology
Lasse F. Voss, Amanda J. Howarth, Thomas R. Wittenborn, Sandra Hummelgaard, Kristian Juul-Madsen, Kristian S. Kastberg, Mathias K. Pedersen, Lisbeth Jensen, Anastasios D. Papanastasiou, Thomas Vorup-Jensen, Kathrin Weyer, Soren E. Degn
Summary: This study investigated the contribution of the extrafollicular pathway to the development of autoimmune diseases. The results showed that blocking the germinal center pathway did not effectively curb autoimmune progression in two mouse models. In addition, in vitro experiments showed that the loss of Bcl-6 prevented the expansion of germinal center B cells and accelerated plasma cell differentiation. Therefore, the extrafollicular pathway plays a key role in the progression of autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Sandra Hummelgaard, Joachim Pold Vilstrup, Camilla Gustafsen, Simon Glerup, Kathrin Weyer
Summary: Lowering blood cholesterol levels is crucial for reducing the risk of ASCVD, and PCSK9 plays a key role in cholesterol metabolism. Inhibiting PCSK9 has been shown to effectively reduce cholesterol levels and mitigate the risk of ASCVD events.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Urology & Nephrology
Cecilie K. Skeby, Sandra Hummelgaard, Camilla Gustafsen, Federica Petrillo, Kathrine P. Frederiksen, Ditte Olsen, Tilde Kristensen, Per Ivarsen, Peder Madsen, Erik I. Christensen, Rikke Nielsen, Henrik Birn, Simon Glerup, Kathrin Weyer
Summary: This article proposes a mechanistic coupling between proteinuria and PCSK9, showing that PCSK9 is a negative regulator of megalin and glomerular damage increases filtration of PCSK9, resulting in escalated proteinuria.
KIDNEY INTERNATIONAL
(2023)
Review
Urology & Nephrology
Sandra Hummelgaard, Kathrin Weyer
Summary: The kidney proximal tubule is an important target tissue of the renin-angiotensin system (RAS). Megalin, as an endocytic multiligand receptor, plays a role in the reabsorption of peptides and proteins from the glomerular ultrafiltrate in the proximal tubule. All major components of RAS are present in the kidney proximal tubules. Recent studies suggest that megalin-mediated reabsorption of liver-derived AGT contributes to renal ANG II levels, potentially affecting renal RAS activity and blood pressure regulation.
Article
Neurosciences
Abdel-Rahman Al-Absi, Per Qvist, Simon Glerup, Connie Sanchez, Jens R. Nyengaard
Summary: The 15q13.3 deletion is associated with neurodevelopmental disorders, and a mouse model has been generated to study this syndrome. The study on the Df(h15q13)/+ mouse model revealed molecular and structural alterations in the medial prefrontal cortex, including decrease in glial cells, deficit of inhibitory markers, and reduced dendritic arborization. These nonneuronal circuit alterations may contribute to the phenotypes seen in the 15q13.3 deletion syndrome.
Article
Physiology
Qidong Ren, Kathrin Weyer, Youssef Rbaibi, Kimberly R. Long, Roderick J. Tan, Rikke Nielsen, Erik Christensen, Catherine J. Baty, Ossama B. Kashlan, Ora A. Weisz
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2020)