Article
Pharmacology & Pharmacy
Hanyu Yang, Mengxiang Su, Ming Liu, Yun Sheng, Liang Zhu, Lu Yang, Ruijing Mu, Jianjun Zou, Xiaodong Liu, Li Liu
Summary: This study found that the decrease in hepatic retinaldehyde (Rald) levels is closely associated with the progression of type 2 diabetes (T2D). By increasing hepatic Rald levels, fasting glycemia can be lowered, hepatic glucogenesis can be inhibited, and glucose metabolism can be improved. These findings highlight the significance of hepatic Rald levels in the progression of T2D.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Gyun-Sik Oh, Si-Ryong Kim, Eun-Sook Lee, Jin Yoon, Min-Kyung Shin, Hyeon Kyoung Ryu, Dong Seop Kim, Seung-Whan Kim
Summary: NCOA6 is a transcriptional coactivator of nuclear receptors and other transcription factors. It regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.
MOLECULES AND CELLS
(2022)
Review
Cell Biology
Yong Yu, Jingying Li, Kaiming Ren
Summary: Metabolic reprogramming often involves changes in metabolic enzyme expression, which not only catalyze intracellular metabolic reactions but also regulate tumor initiation and development through molecular events. Phosphoenolpyruvate carboxykinases (PCKs) are key enzymes in gluconeogenesis and play important roles in metabolic adaptation, immune response, and signaling pathways for tumor progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Plant Sciences
Bruno E. Rojas, Matias D. Hartman, Carlos M. Figueroa, Alberto A. Iglesias
Summary: The study analyzed the proteolysis of PEPCK1 in germinating Arabidopsis thaliana seedlings, and found that shorter versions of the protein may be generated by metacaspase-9. Truncated mutants Delta 19 and Delta 101 of AthPEPCK1 exhibited similar kinetic parameters, but activation by malate and inhibition by glucose 6-phosphate were abolished in the .101 mutant. This proteolysis is proposed to adapt the sensitivity to allosteric regulation during the transition from sink to source in germinating seedlings.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Medicine, Research & Experimental
Mohsin Rahim, Clinton M. Hasenour, Tomasz K. Bednarski, Curtis C. Hughey, David H. Wasserman, Jamey D. Young
Summary: The study demonstrates that the kidney can compensate for impaired hepatic glucose production by increasing renal glucose production and gluconeogenesis. Hepatic gluconeogenesis was reduced in KO mice, but whole-body glucose production and arterial glucose were unaffected, leading to a compensatory rise in renal glucose production and gluconeogenesis.
Article
Endocrinology & Metabolism
Amandine Gautier-Stein, Julien Chilloux, Maud Soty, Bernard Thorens, Christophe Place, Carine Zitoun, Adeline Duchampt, Lorine Da Costa, Fabienne Rajas, Christophe Lamaze, Gilles Mithieux
Summary: This study reveals a new pathway of glucose production through Cav1-dependent trafficking of G6PC1 to the plasma membrane, contributing to hepatic glucose production and glucose homeostasis.
MOLECULAR METABOLISM
(2023)
Article
Cell Biology
Wenxiang Hu, Chunjie Jiang, Mindy Kim, Wenjian Yang, Kun Zhu, Dongyin Guan, Wenjian Lv, Yang Xiao, Jessica R. Wilson, Daniel J. Rader, Ching-Hon Pui, Mary Relling, Mitchell A. Lazar
Summary: The study revealed cell type-specific and individual-specific responses to glucocorticoids, attributed to single-nucleotide polymorphisms that altered the binding motifs of the glucocorticoid receptor or its cooperating factors. Additionally, genetic variants affecting chromatin accessibility or structure were found to modulate the response to glucocorticoids. These genetic variations influenced glucocorticoid-induced metabolic perturbations and were associated with increased serum glucose, lipids, and body mass in subjects on glucocorticoid therapy.
Article
Physiology
Thomas Verissimo, Delal Dalga, Gregoire Arnoux, Imene Sakhi, Anna Faivre, Hannah Auwerx, Soline Bourgeois, Deborah Paolucci, Quentin Gex, Joseph M. Rutkowski, David Legouis, Carsten A. Wagner, Andrew M. Hall, Sophie de Seigneux
Summary: Phosphoenolpyruvate carboxykinase 1 (PCK1) plays an important role in maintaining normal tubular physiology, lactate, and glucose homeostasis in the kidney. It regulates acid-base balance and ammoniagenesis. Downregulation of PCK1 during renal injury impairs renal function, making it a potential therapeutic target in renal disease.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yang Liu, Ling Li, Zhuo Yang, Li-xi Liao, Xiao-jun Yao, Peng-fei Tu, Ke-wu Zeng
Summary: Aberrant PCK2 overexpression is associated with poor prognosis and shorter survival in hepatocellular carcinoma (HCC). This study identified a natural-derived small-molecule CuB as a selective PCK2 inhibitor, which can reprogram lipid metabolism and control mitochondrial dynamics for cancer treatment.
CHEMICAL COMMUNICATIONS
(2023)
Article
Oncology
Ke Tang, Liyan Zhu, Jie Chen, Dianheng Wang, Liping Zeng, Chen Chen, Liang Tang, Li Zhou, Keke Wei, Yabo Zhou, Jiadi Lv, Yuying Liu, Huafeng Zhang, Jingwei Ma, Bo Huang
Summary: Hypoxia promotes the growth of breast tumor-repopulating cells through metabolic reprogramming mediated by PCK1. This metabolic mechanism is absent in differentiated breast tumor cells, and targeting PCK1 synergizes with paclitaxel to reduce the growth of triple-negative breast cancer.
Article
Multidisciplinary Sciences
Maria J. Gonzalez-Rellan, Marcos F. Fondevila, Uxia Fernandez, Amaia Rodriguez, Marta Varela-Rey, Christelle Veyrat-Durebex, Samuel Seoane, Ganeko Bernardo, Fernando Lopitz-Otsoa, David Fernandez-Ramos, Jon Bilbao, Cristina Iglesias, Eva Novoa, Cristina Ameneiro, Ana Senra, Daniel Beiroa, Juan Cunarro, Maria D. P. Chantada-Vazquez, Maria Garcia-Vence, Susana B. Bravo, Natalia Da Silva Lima, Begona Porteiro, Carmen Carneiro, Anxo Vidal, Sulay Tovar, Timo D. Muller, Johan Ferno, Diana Guallar, Miguel Fidalgo, Guadalupe Sabio, Stephan Herzig, Won Ho Yang, Jin Won Cho, Maria Luz Martinez-Chantar, Roman Perez-Fernandez, Miguel Lopez, Carlos Dieguez, Jose M. Mato, Oscar Millet, Roberto Coppari, Ashwin Woodhoo, Gema Fruhbeck, Ruben Nogueiras
Summary: The O-GlcNAcylation of p53 in the liver plays a crucial role in the physiological regulation of glucose homeostasis by controlling the expression of phosphoenolpyruvate carboxykinase.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sarah A. E. Barwell, Ramona Duman, Armin Wagner, Todd Holyoak
Summary: Phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme involved in glucose metabolism, catalyzing a key step in gluconeogenesis. The preferential synthesis of phosphoenolpyruvate (PEP) from oxaloacetic acid (OAA) catalyzed by PEPCK in vivo is facilitated by anion-mediated enzyme inhibition. The binding of ubiquitous anions like chloride restricts the enzyme to function in the direction of PEP synthesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Yu-Xian Zhu, Hai-Qing Hu, Mei-Ling Zuo, Li Mao, Gui-Lin Song, Tao-Ming Li, Li-Chen Dong, Zhong-Bao Yang, Md Sayed Ali Sheikh
Summary: Oxymatrine effectively prevents insulin resistance and gluconeogenesis, potentially through the regulation of PEPCK and G6Pase expression and AKT phosphorylation in the liver.
BIOMEDICAL REPORTS
(2021)
Review
Endocrinology & Metabolism
Shuo Yu, Simin Meng, Meixiang Xiang, Hong Ma
Summary: PCK enzyme plays important roles beyond gluconeogenesis, including in the development of obesity, cardiac hypertrophy, stroke, and cancer. The expression of PCK is precisely controlled by a complex regulatory network involving epigenetic regulation, transcription regulation, and posttranscription regulation. Understanding the regulation of PCK may lead to the development of strategies to treat metabolic dysfunction.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Renato Martins da Silva, Wagner Oliveira Vital, Ronald Sodre Martins, Jorge Moraes, Helga Gomes, Christiano Calixto, Satoru Konnai, Kazuhiko Ohashi, Itabajara da Silva Vaz Jr, Carlos Logullo
Summary: The study identified two PEPCK isoforms in Aedes aegypti through sequence alignment, protein modeling, and transcription analysis, revealing differential activity and transcriptional profiles during oogenesis and embryogenesis. These findings enhance our understanding of mosquito physiology and may lead to the development of new methods for controlling A. aegypti.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2021)