Review
Endocrinology & Metabolism
Jonathan S. S. Bogan
Summary: This article reviews recent advances in the mechanism of GLUT4 glucose transporter mobilization to enhance glucose uptake in response to insulin stimulation. The processing of TUG proteins plays a central role in regulating this process, with endoproteolytic cleavage of TUG mediated by the Usp25m protease being a key step in vesicle release. TUG processing also affects gene expression related to fatty acid oxidation and thermogenesis, further regulating energy metabolism.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Brent A. Fujimoto, Madison Young, Nicole Nakamura, Herena Ha, Lamar Carter, Matthew W. Pitts, Daniel Torres, Hye-Lim Noh, Sujin Suk, Jason K. Kim, Noemi Polgar
Summary: This study demonstrates the importance of EXOC5 and the exocyst in insulin-stimulated glucose uptake in skeletal muscle cells. Deficiency of EXOC5 in skeletal muscle cells led to elevated fasting glucose levels, impaired glucose tolerance, and lower energy expenditure in mice. Overall, these findings suggest that EXOC5 and the exocyst play a crucial role in regulating glucose homeostasis in vivo.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Dougall Norris, Pengyi Yang, Sung-Young Shin, Alison L. Kearney, Hani Jieun Kim, Thomas Geddes, Alistair M. Senior, Daniel J. Fazakerley, Lan K. Nguyen, David E. James, James G. Burchfield
Summary: The study found that intercellular heterogeneity in insulin signaling primarily stems from variance in gene/protein expression between cells rather than within cells. This single-cell heterogeneity leads to differences in population response to insulin signaling.
Article
Biochemistry & Molecular Biology
Roni Rahimi, Israel Malek, Tali Lerrer-Goldshtein, Yoav Elkis, Irit Shoval, Avi Jacob, Sally Shpungin, Uri Nir
Summary: The study investigates the regulatory role of TMF1 in GLUT4-mediated glucose uptake and insulin-directed functioning, showing that TMF1 is essential for the formation of insulin responsive, GLUT4-containing vesicles. Absence of TMF1 leads to impaired glucose uptake, resulting in hyperglycemia and decreased body weight in mice, indicating a novel effector in insulin-regulated glucose homeostasis.
Article
Cell Biology
Hannah L. Black, Rachel Livingstone, Cynthia C. Mastick, Mohammed Al Tobi, Holly Taylor, Angeline Geiser, Laura Stirrat, Dimitrios Kioumourtzoglou, John R. Petrie, James G. Boyle, Nia J. Bryant, Gwyn W. Gould
Summary: The knockout of syntaxin-4 in 3T3-L1 adipocytes was found to significantly reduce insulin-stimulated glucose transport and adiponectin secretion, but had only modest effects on the translocation capacity of the cells and the exocytic and endocytic rates of GLUT4.
JOURNAL OF CELL SCIENCE
(2022)
Article
Cell Biology
Yifei Pei, Shuning Lv, Yong Shi, Jingwen Jia, Mengru Ma, Hailong Han, Rongying Zhang, Jieqiong Tan, Xinjun Zhang
Summary: The small GTPase RAB21 plays a critical role in regulating endosomal dynamics and maintaining cellular energy homeostasis. Depletion of RAB21 leads to mis-sorting of glucose transporter SLC2A1 to lysosomes, affecting glucose uptake and increasing autophagic flux. RAB21 depletion also enhances lysosome function.
Review
Geriatrics & Gerontology
Shun Yoshida, Takafumi Hasegawa
Summary: Retromer is a protein complex involved in retrograde cargo sorting, which is closely related to neurodegenerative diseases. Dysfunction of retromer has been found to be involved in the pathogenesis of Alzheimer's Disease and Parkinson's disease. Targeting retromer may present a potential therapeutic strategy for these neurodegenerative diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ruiju Wang, Ruixuan Wang, Mengmeng Liu, Weiwei Yuan, Zhiying Zhao, Xiaoqian Liu, Yameng Peng, Xiaorui Yang, Yu Sun, Wenqiang Tang
Summary: BZR1, a key transcription factor in the brassinosteroid signaling pathway, is tightly regulated by phosphorylation and subcellular localization; it can be rapidly recruited from the cytoplasm to the nucleus by BR treatment, and its protein abundance is regulated by two distinct turnover mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Pharmacology & Pharmacy
Lokender Kumar, Whitney Vizgaudis, Judith Klein-Seetharaman
Summary: The insulin receptor plays a vital role in regulating nutrient balance and is an attractive target for diabetes and metabolic syndrome treatment. This study investigates the pharmacology of the insulin receptor through two mechanisms: activation by insulin mimetics and inhibition of its enzymatic activity. Recent progress in cryoelectron microscopy allows for a detailed understanding of the initial insulin ligand binding events. The researchers conducted a comprehensive docking study to gain structural insights into the insulin receptor pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Morris F. White, C. Ronald Kahn
Summary: The discovery and application of insulin marked a major turning point in medical history, playing a crucial role in blood glucose regulation and the treatment of diseases like diabetes.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Peng Huang, Hannah Abacka, Daniel Varela, Raminta Venskutonyte, Lotta Happonen, Jonathan S. Bogan, Pontus Gourdon, Mahmood R. Amiry-Moghaddam, Ingmar Andre, Karin Lindkvist-Petersson
Summary: Insulin stimulation leads to dissociation of GLUT4 from the intracellular protein TUG, promoting glucose uptake. The study discovers that ASPL forms a complex with GLUT4 in human cells, contributing to the regulation of GLUT4 trafficking.
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
Endocrinology & Metabolism
Kazuhisa Watanabe, Ayumi Matsumoto, Hidetoshi Tsuda, Sadahiko Iwamoto
Summary: The study revealed that N4bp2l1 is a novel target gene of FoxO1, with its expression being controlled by insulin-mediated regulation of FoxO1. N4BP2L1 interacts with dynactin, which binds to the microtubule motor dynein, indicating its involvement in GLUT4 trafficking and glucose uptake in 3T3-L1 adipocytes. These findings suggest that N4BP2L1 plays a role in adipocyte homeostasis by affecting GLUT4-mediated glucose uptake and the insulin signaling pathway.
JOURNAL OF DIABETES INVESTIGATION
(2021)
Article
Cell Biology
Jie Pan, Suchart Kothan, Laihao Liu, Aye Thidar Moe, Liwei Dong, Yanan Sun, Yiyi Yang
Summary: Our study demonstrated that autophagy is positively related to the dedifferentiation of 3T3-L1 adipocytes and is regulated through the insulin-PI3K-AKT-mTORC1-autophagy pathway. Additionally, autophagy may have a certain degree of negative feedback affect on the insulin signaling of 3T3-L1 cells.
CELLULAR SIGNALLING
(2021)
Article
Multidisciplinary Sciences
Hongbo Li, Ruihua Huang, Yanglan Liao, Shuhong Yang, Bojin Feng, Hongting Qin, Jun Zhou, Yonglun Zeng, Jinbo Shen, Xiaohong Zhuang, Liwen Jiang, Marisa S. Otegui, Shengchun Zhang, Caiji Gao
Summary: The study identifies a plant-specific endosomal regulator, BLISTER (BLI), that interacts with the retromer complex and plays a crucial role in regulating endosomal trafficking in plants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)