ArticleAmerican journal of physiology. Endocrinology and metabolism2012
Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 107 citations in OpenAlex.
- Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women.PloS one · 2016Trial
- Trial
- AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy.Acta physiologica (Oxford, England) · 2026Article
- Proteotoxic Stress Triggers Autophagy-Mediated AS160 Degradation and Metabolic Reprogramming in Colorectal Cancer.ACS omega · 2026Article
- Exofacial Epitope-Specific Antibodies Detect GLUT4 Translocation in Adult Human, Rat, and Mouse Skeletal Muscle.Diabetes · 2026Article
- Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.Nature metabolism · 2024Article
- Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.Journal of cell science · 2023Article
- Akt substrate of 160 kDa is essential for the calorie restriction-induced increase in insulin-stimulated glucose uptake by skeletal muscle of female rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2023Article
- Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion.Cardiovascular diabetology · 2023Article
- Sex Differences in Glucose Homeostasis.Handbook of experimental pharmacology · 2023Article
- Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Normalization of maternal adiponectin in obese pregnant mice prevents programming of impaired glucose metabolism in adult offspring.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.The Biochemical journal · 2022Article
- Estradiol replacement improves high-fat diet-induced insulin resistance in ovariectomized rats.Physiological reports · 2022Article
- AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake.Cell death and differentiation · 2021Article
- AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021Review
- Role of Akt isoforms in neuronal insulin signaling and resistance.Cellular and molecular life sciences : CMLS · 2021Article
- Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers.Diabetologia · 2021Article
- Article
- Insulin-promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10.Molecular biology of the cell · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.
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