Review
Genetics & Heredity
Wei Zhang, Yan-Mei Sang
Summary: Congenital hyperinsulinism (CHI) is a major cause of persistent and recurrent hypoglycemia in infancy and childhood. KATP-HI is the most common and severe subtype, accounting for 40-50% of CHI cases, while SCHAD-HI is a rare subtype caused by homozygous mutations in the HADH gene, accounting for less than 1% of all CHI cases. This review provides a systematic description of the genetic pathogenesis and current progress in the diagnosis and treatment of SCHAD-HI.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Neurosciences
Karim Gariani, Antoine Klauser, Maria Isabel Vargas, Francois Lazeyras, Christel Tran
Summary: Hyperinsulinism/hyperammonemia syndrome (HI/HA) is caused by activating mutations in the GLUD1 gene, leading to insulin overproduction and chronic asymptomatic hyperammonemia. Brain magnetic resonance imaging in HI/HA patients shows differences in brain biochemistry compared to other hyperammonemia disorders, with normal levels of combined glutamate and glutamine.
Article
Biotechnology & Applied Microbiology
Yan Zhou, Yifeng Wei, Li Jiang, Yan Zhang, Xinan Jiao
Summary: This study reports the discovery of a novel pathway for the degradation of (S)-3-hydroxybutyrate, a ketone body produced in the liver during glucose starvation. A stereospecific enzyme called (S)-3-hydroxylbutyrate dehydrogenase (3SHBDH) was identified and characterized, and its function in the metabolism of (S)-3-hydroxybutyrate was elucidated. This finding has significant implications for understanding the metabolism of (S)-3-hydroxybutyrate and its potential applications in diagnostics and the chemicals industry.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Endocrinology & Metabolism
Paul S. Thornton, Diva D. De Leon, Susann Empting, David Zangen, David M. Kendall, Sune Birch, Eva Boge, Jelena Ivkovic, Indraneel Banerjee
Summary: This study evaluated the efficacy and safety of continuous subcutaneous infusion of dasiglucagon as an add-on treatment for children with CHI and persistent hypoglycemia. Dasiglucagon was found to significantly reduce the frequency and severity of hypoglycemic episodes, and was well tolerated.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Review
Genetics & Heredity
Qiao Zeng, Yan-Mei Sang
Summary: Congenital hyperinsulinism (CHI) is a genetically heterogeneous disease characterized by excessive insulin secretion and increased serum insulin concentration, leading to intractable, persistent hypoglycemia. Glutamate dehydrogenase hyperinsulinism (GDH-HI) is the second most common type of CHI, caused by mutations in the glutamate dehydrogenase 1 gene. This review aims to summarize the genetic mechanisms, diagnosis, and treatment progress of GDH-HI. Early diagnosis and treatment are crucial in preventing long-term neurological complications in children with GDH-HI.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Nutrition & Dietetics
Ana Paula Dantas Ribeiro, Amanda Gomes Pereira, Marcia Cristina B. S. Todo, Anderson Seiji Soares Fujimori, Priscila Portugal dos Santos, Danielle Dantas, Ana Angelica Fernandes, Silmeia Garcia Zanati, Neuza Mariko Aymoto Hassimotto, Leonardo Antonio Mamede Zornoff, Paula Schmidt Azevedo, Marcos Ferreira Minicucci, Sergio A. R. Paiva, Bertha Furlan Polegato
Summary: The study evaluated the effects of Pera and Moro orange juices on cardiac remodeling induced by doxorubicin. Both juices were found to reduce oxidative stress, improve ventricular function, and normalize myocardial energy metabolism. Moro orange juice showed a more significant effect in modifying energy metabolism compared to Pera orange juice.
Article
Endocrinology & Metabolism
Kelly Velasco, Johanna L. St-Louis, Henrikke N. Hovland, Nels Thompson, Asta Ottesen, Man Hung Choi, Line Pedersen, Pal R. Njolstad, Thomas Arnesen, Karianne Fjeld, Ingvild Aukrust, Line M. Myklebust, Anders Molven
Summary: Functional evaluation of 16 SCHAD missense variants revealed that CHI-associated variants may lead to protein instability or impaired enzymatic activity. Rare variants identified in general populations do not show functional effects on the protein.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Endocrinology & Metabolism
Miguel Angel De los Santos-La Torre, Carlos Manuel Del Aguila-Villar, Luis Romulo Lu-de Lama, Oswaldo Nunez-Almache, Eliana Manuela Chavez-Tejada, Oscar Antonio Espinoza-Robles, Paola Marianella Pinto-Ibarcena, Martha Rosario Calagua-Quispe, Pamela Miluska Azabache-Tafur, Rosa Maria Tucto-Manchego
Summary: Congenital hyperinsulinism is a heterogeneous disorder with variable clinical phenotypes caused by pathogenic variants in multiple genes. Hyperinsulinism-hyperammonemia syndrome, characterized by fasting and postprandial hypoglycemia and mild hyperammonemia with associated neurological abnormalities, is the second most common cause of the disease. We present two Peruvian children with epilepsy who were found to have missense mutations in the GLUD1 gene, which responded well to diazoxide therapy, and highlight the importance of timely diagnosis for proper management.
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
(2023)
Article
Chemistry, Medicinal
Jian Zhao, Shimiao Wang, Sun Hee Kim, Sangdon Han, Elizabeth Rico-Bautista, Emmanuel Sturchler, Julie Nguyen, Hannah Tan, Christine Staley, Ana Karin Kusnetzow, Stephen F. Betz, Michael Johns, Lance Goulet, Rosa Luo, Melissa Fowler, Jon Athanacio, Stacy Markison, R. Scott Struthers, Yunfei Zhu
Summary: The activation of SST5 receptors strongly inhibits insulin secretion, and a newly discovered nonpeptide selective SST5 agonist shows potential for managing blood glucose levels in congenital HI patients. The agonist exhibits excellent potency and selectivity against other receptors and has promising pharmacokinetic profiles in animal models.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Nutrition & Dietetics
Alejandra Abascal-Saiz, Eva Fuente-Luelmo, Maria Haro, Victoria Fioravantti, Eugenia Antolin, Maria P. Ramos-Alvarez, Jose L. Bartha
Summary: The mRNA expression of FAO enzymes in the placenta is lower in pre-eclampsia, with more significant reductions observed in severe, early-onset, and intrauterine growth restriction (IUGR) cases, particularly on the fetal side.
Review
Biochemistry & Molecular Biology
Yunfei Bian, Wei Hou, Xinrou Chen, Jinzhang Fang, Ning Xu, Benfang Helen Ruan
Summary: This perspective summarizes the progress in the discovery and development of GDH inhibitors for the treatment of Hyperinsulinism-hyperammonemia syndrome (HHS). It explores the pathogenesis of HHS and the potential binding sites, screening methods, and research models for GDH inhibitors. Future therapeutic perspectives and research directions are provided.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Huan Peng, Min Xie, Xiaoyi Zhong, Yongshao Su, Xue Qin, Qingping Xu, Sigui Zhou
Summary: Short-chain acyl-CoA dehydrogenase (SCAD), an enzyme involved in fatty acid oxidation, regulates pathological cardiac hypertrophy and fibrosis. Its coenzyme FAD plays a crucial role in myocardial energy metabolism. Insufficient riboflavin intake can lead to symptoms similar to SCAD deficiency or FAD gene abnormalities, but the effect of riboflavin on cardiac hypertrophy and fibrosis is unclear. In this study, riboflavin was found to increase SCAD expression, ATP content, and FAD content, while decreasing free fatty acids. This led to improvements in induced hypertrophy and fibrosis in cardiomyocytes and cardiac fibroblasts. In animal experiments, riboflavin improved TAC-induced hypertrophy and fibrosis by increasing SCAD expression and energy metabolism. These findings suggest that riboflavin may be a potential treatment for pathological cardiac hypertrophy and fibrosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Kara E. E. Boodhansingh, Elizabeth Rosenfeld, Katherine Lord, N. Scott Adzick, Tricia Bhatti, Arupa Ganguly, Diva D. D. De Leon, Charles A. A. Stanley
Summary: The study found that low-level mosaic mutations in the GLUD1 gene may be the underlying molecular mechanism in some children with HI who have negative genetic testing in peripheral blood DNA.
HORMONE RESEARCH IN PAEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Hyeoncheol Francis Son, Jae-Woo Ahn, Jiyeon Hong, Jihye Seok, Kyeong Sik Jin, Kyung-Jin Kim
Summary: By determining the crystal structure of multi-functional enoyl-CoA hydratase from Cupriavidus necator H16 (CnFadB), our study provides insights into fatty acid metabolism in this bacterium. Unlike other known enzymes, CnFadB functions as a monomer and the non-sequential action of FadA and FadB appears to impact PHA synthesis/degradation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Peripheral Vascular Disease
Xiaoyi Zhong, Zhonghong Li, Qingping Xu, Huan Peng, Yongshao Su, Kang Le, Zhaohui Shu, Yingqin Liao, Zhichao Ma, Xuediao Pan, Suowen Xu, Sigui Zhou
Summary: This study investigated the possible role of short-chain acyl-CoA dehydrogenase (SCAD) in hypertension associated vascular remodelling. The expression of SCAD decreased with age and aerobic exercise training increased its expression and decreased vascular remodelling. SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and hypertensive patients' aortas. SCAD acts as a negative regulator of vascular remodelling and may be a potential therapeutic target.
JOURNAL OF HYPERTENSION
(2023)
Editorial Material
Pediatrics
Charles A. Stanley, Paul J. Rozance, Paul S. Thornton, Diva D. De Leon, Deborah Harris, Morey W. Haymond, Khalid Hussain, Lynne L. Levitsky, Mohammad H. Murad, Rebecca A. Simmons, Mark A. Sperling, David A. Weinstein, Neil H. White, Joseph I. Wolfsdorf
JOURNAL OF PEDIATRICS
(2015)
Article
Cell Biology
Sharona Tornovsky-Babeay, Daniela Dadon, Oren Ziv, Elhanan Tzipilevich, Tehila Kadosh, Rachel Schyr-Ben Haroush, Ayat Hija, Miri Stolovich-Rain, Judith Furth-Lavi, Zvi Granot, Shay Porat, Louis H. Philipson, Kevan C. Herold, Tricia R. Bhatti, Charles Stanley, Frances M. Ashcroft, Peter In't Veld, Ann Saada, Mark A. Magnuson, Benjamin Glaser, Yuval Dor
Article
Endocrinology & Metabolism
Richard G. Kibbey, Cheol Soo Choi, Hui-Young Lee, Over Cabrera, Rebecca L. Pongratz, Xiaojian Zhao, Andreas L. Birkenfeld, Changhong Li, Per-Olof Berggren, Charles Stanley, Gerald I. Shulman
Article
Biochemistry & Molecular Biology
Changhong Li, Chengyang Liu, Itzhak Nissim, Jie Chen, Pan Chen, Nicolai Doliba, Tingting Zhang, Ilana Nissim, Yevgeny Daikhin, David Stokes, Marc Yudkoff, Michael J. Bennett, Charles A. Stanley, Franz M. Matschinsky, Ali Naji
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Endocrinology & Metabolism
K. E. Snider, S. Becker, L. Boyajian, S. -L. Shyng, C. MacMullen, N. Hughes, K. Ganapathy, T. Bhatti, C. A. Stanley, A. Ganguly
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2013)
Article
Endocrinology & Metabolism
Cresio Alves, Julia Constanca, Diva D. De Leon, Kara Snider, Charles Stanley
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
(2013)
Article
Pediatrics
William H. Peranteau, Andrew A. Palladino, Tricia R. Bhatti, Susan A. Becker, Lisa J. States, Charles A. Stanley, N. Scott Adzick
JOURNAL OF PEDIATRIC SURGERY
(2013)
Article
Pediatrics
Pablo Laje, Andrew A. Palladino, Tricia R. Bhatti, Lisa J. States, Charles A. Stanley, N. Scott Adzick
JOURNAL OF PEDIATRIC SURGERY
(2013)
Article
Pediatrics
Pablo Laje, Lisa J. States, Hongming Zhuang, Susan A. Becker, Andrew A. Palladino, Charles A. Stanley, N. Scott Adzick
JOURNAL OF PEDIATRIC SURGERY
(2013)
Editorial Material
Pediatrics
Colin P. Hawkes, Charles A. Stanley
JOURNAL OF PEDIATRICS
(2014)
Review
Radiology, Nuclear Medicine & Medical Imaging
Bjoern A. Blomberg, Mateen C. Moghbel, Babak Saboury, Charles A. Stanley, Abass Alavi
MOLECULAR IMAGING AND BIOLOGY
(2013)
Article
Biochemistry & Molecular Biology
Ming Li, Changhong Li, Aron Allen, Charles A. Stanley, Thomas J. Smith
NEUROCHEMICAL RESEARCH
(2014)
Article
Medicine, General & Internal
L. C. Tegtmeyer, S. Rust, M. van Scherpenzeel, B. G. Ng, M. -E. Losfeld, S. Timal, K. Raymond, P. He, M. Ichikawa, J. Veltman, K. Huijben, Y. S. Shin, V. Sharma, M. Adamowicz, M. Lammens, J. Reunert, A. Witten, E. Schrapers, G. Matthijs, J. Jaeken, D. Rymen, T. Stojkovic, P. Laforet, F. Petit, O. Aumaitre, E. Czarnowska, M. Piraud, T. Podskarbi, C. A. Stanley, R. Matalon, P. Burda, S. Seyyedi, V. Debus, P. Socha, J. Sykut-Cegielska, F. van Spronsen, L. de Meirleir, P. Vajro, T. DeClue, C. Ficicioglu, Y. Wada, R. A. Wevers, D. Vanderschaeghe, N. Callewaert, R. Fingerhut, E. van Schaftingen, H. H. Freeze, E. Morava, D. J. Lefeber, T. Marquardt
NEW ENGLAND JOURNAL OF MEDICINE
(2014)
Article
Endocrinology & Metabolism
Tingting Zhang, Pan Chen, Charles A. Stanley, Toshinori Hoshi, Changhong Li
Review
Endocrinology & Metabolism
Paul S. Thornton, Charles A. Stanley, Diva D. De Leon
Summary: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. This field has made significant advancements, including the development of insulin radioimmunoassay, the discovery of different genetic subtypes, and the recognition and treatment of focal hyperinsulinism. However, treatment options for some patients remain limited, calling for further development.
HORMONE RESEARCH IN PAEDIATRICS
(2022)