ArticleCell metabolism2011
Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking.
Article in Cell metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 157 citations in OpenAlex.
- Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2012Trial
- Disruption of RNA metabolism and its impact on protein homeostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- WNK1 Phosphorylation Sites in TBC1D1 and TBC1D4 Modulate Cell-Surface Abundance of GLUT1.Cells · 2026Article
- TBC1D4-Related Monogenic Diabetes: Molecular Mechanisms, Clinical Recognition, and Therapeutic Implications.Journal of diabetes · 2026Review
- Enhanced Energy Metabolism and Developmental Signaling in Neonatal Brains of Female Piglets Parenterally Fed with 18-Carbon n-3 Fatty Acid-Based Vegaven Compared with Fish Oil-Containing Lipid Emulsion.Current developments in nutrition · 2026Article
- Golgi-associated TRAF6 as a regulator of protein convertase FURIN for insulin receptor precursor processing.Science China. Life sciences · 2025Article
- TBC1D1 functions as a negative regulator of satellite cells for muscle regeneration.Nature communications · 2025Article
- Nuclear entry of AS160 as a transcriptional regulator of satellite cells for muscle regeneration.Nature communications · 2025Article
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 14-3-3ζ allows for adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.Molecular metabolism · 2025Article
- Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.Nature metabolism · 2024Article
- AS160 is a lipid-responsive regulator of cardiac CaNature communications · 2024Article
- TBC1 domain-containing proteins are frequently involved in triple-negative breast cancers in connection with the induction of a glycolytic phenotype.Cell death & disease · 2024Article
- Fine-tuning AMPK in physiology and disease using point-mutant mouse models.Disease models & mechanisms · 2024Review
- Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.International journal of molecular sciences · 2024Review
- Phosphorylation of AS160-serine 704 is not essential for exercise-increase in insulin-stimulated glucose uptake by skeletal muscles from female or male rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- Independent and combined effects of calorie restriction and AICAR on glucose uptake and insulin signaling in skeletal muscles from 24-month-old female and male rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2024Article
- A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.Frontiers in physiology · 2024Review
- Is 14-3-3 the Combination to Unlock New Pathways to Improve Metabolic Homeostasis and β-Cell Function?Diabetes · 2023Review
- AS160 expression, but not AS160 Serine-588, Threonine-642, and Serine-704 phosphorylation, is essential for elevated insulin-stimulated glucose uptake by skeletal muscle from female rats after acute exercise.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
AS160 has emerged as a key player in insulin-mediated glucose transport through controlling GLUT4 trafficking, which is thought to be regulated by insulin-stimulated phosphorylation of sites including the 14-3-3 binding phospho-Thr649 (equivalent to Thr642 in human AS160). To define physiological roles of AS160-Thr649 phosphorylation and 14-3-3 binding in glucose homeostasis, we substituted this residue by a nonphosphorylatable alanine by knockin mutation in mice. The mutant protein was expressed at normal levels, while insulin-stimulated AS160 binding to 14-3-3s was abolished in homozygous knockin mice. These animals displayed impaired glucose disposal and insulin sensitivity, which were associated with decreased glucose uptake in vivo. Insulin-stimulated glucose transport and cell surface GLUT4 content were reduced in isolated muscles, but not in adipocytes. These results provide genetic evidence that insulin-induced AS160-Thr649 phosphorylation and/or its binding to 14-3-3 play an important role in regulating whole-body glucose homeostasis, at least in part through regulating GLUT4 trafficking in muscle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.