Regulation of glucose transport by insulin: traffic control of GLUT4
Abstract
Despite daily fasting and feeding, plasma glucose levels are normally maintained within a narrow range owing to the hormones insulin and glucagon. Insulin increases glucose uptake into fat and muscle cells through the regulated trafficking of vesicles that contain glucose transporter type 4 (GLUT4). New insights into insulin signalling reveal that phosphorylation events initiated by the insulin receptor regulate key GLUT4 trafficking proteins, including small GTPases, tethering complexes and the vesicle fusion machinery. These proteins, in turn, control GLUT4 movement through the endosomal system, formation and retention of specialized GLUT4 storage vesicles and targeted exocytosis of these vesicles. Understanding these processes may help to explain the development of insulin resistance in type 2 diabetes and provide new potential therapeutic targets.
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RalA is transiently activated by insulin in brown adipocytes in response to short-term AKT activation.
“RalA is transiently activated by insulin in brown adipocytes in response to short-term AKT activation 46,47 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [47]
The Reps1-Ralbp1-RalA module constitutes an integral segment of the Ral-dependent exocytic pathway, which operates in parallel with the Rab-dependent pathway in mediating cargo exocytosis and maintaining surface protein homeostasis.
“The Reps1-Ralbp1-RalA module constitutes an integral segment of the Ral-dependent exocytic pathway, which operates in parallel with the Rab-dependent pathway in mediating cargo exocytosis and maintaining surface protein homeostasis (11, 59).”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [59]
Cites
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326 · see citing works
Self-citationAdipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · see citing works
Glucose transporters in the 21st Century
Thorens, B., & Mueckler, M. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00712.2009 · Cited by 1,013 · see citing works
Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration
Polak, P., Cybulski, N., Feige, J. N., Auwerx, J., Rüegg, M. A., & Hall, M. N. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.003 · Cited by 480 · see citing works
Lazar, D. F., Wiese, R. J., Brady, M. J., Mastick, C. C., Waters, S. B., Yamauchi, K., Pessin, J. E., Cuatrecasas, P., & Saltiel, A. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.35.20801 · Cited by 396 · see citing works
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Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Nutrient-sensing mechanisms and pathways
Efeyan, A., Comb, W. C., & Sabatini, D. M. (2015) · Nature · doi:10.1038/nature14190 · Cited by 1,110 · see citing works
Biochemical and cellular properties of insulin receptor signalling
Haeusler, R. A., McGraw, T. E., & Accili, D. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.89 · Cited by 739 · see citing works
Exercise Promotes Healthy Aging of Skeletal Muscle
Cartee, G. D., Hepple, R. T., Bamman, M. M., & Zierath, J. R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.007 · Cited by 483 · see citing works
Genetic architecture: the shape of the genetic contribution to human traits and disease
Timpson, N. J., Greenwood, C. M. T., Soranzo, N., Lawson, D. J., & Richards, J. B. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.101 · Cited by 434 · see citing works
The cell biology of systemic insulin function
Tokarz, V. L., MacDonald, P. E., & Klip, A. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201802095 · Cited by 471 · see citing works
Insulin signaling in health and disease
Saltiel, A. R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142241 · Cited by 446 · see citing works
Self-citationBenner, C., van der Meulen, T., Cacéres, E., Tigyi, K., Donaldson, C. J., & Huising, M. O. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-620 · Cited by 302 · see citing works
Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY‐876
Siebeneicher, H., Cleve, A., Rehwinkel, H., Neuhaus, R., Heisler, I., Müller, T., Bauser, M., & Buchmann, B. (2016) · ChemMedChem · doi:10.1002/cmdc.201600276 · Cited by 294 · see citing works
MicroRNAs in Metabolic Disease
Fernández-Hernando, C., Ramírez, C. M., Goedeke, L., & Suárez, Y. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300144 · Cited by 257 · see citing works
Organelle-Specific Initiation of Autophagy
Sica, V., Galluzzi, L., Bravo-San Pedro, J. M., Izzo, V., Maiuri, M. C., & Kroemer, G. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.021 · Cited by 205 · see citing works
Šestan, M., Marinović, S., Kavazović, I., Cekinović, Đ., Wueest, S., Turk Wensveen, T., Brizić, I., Jonjić, S., Konrad, D., Wensveen, F. M., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.05.005 · Cited by 189 · see citing works
Exercise and regulation of carbohydrate metabolism
Mul, J. D., Stanford, K. I., Hirshman, M. F., & Goodyear, L. J. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.020 · Cited by 151 · see citing works
Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle
Perrin, L., Loizides-Mangold, U., Chanon, S., Gobet, C., Hulo, N., Isenegger, L., Weger, B. D., Migliavacca, E., Charpagne, A., Betts, J. A., et al. (2018) · eLife · doi:10.7554/elife.34114 · Cited by 139 · see citing works
Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives
Das, D. K., Graham, Z. A., & Cardozo, C. P. (2020) · Acta Physiologica · doi:10.1111/apha.13367 · Cited by 129 · see citing works
Effects of aldosterone on insulin sensitivity and secretion
Luther, J. M. (2014) · Steroids · doi:10.1016/j.steroids.2014.08.016 · Cited by 114 · see citing works
Metabolic control by AMPK in white adipose tissue
Göransson, O., Kopietz, F., & Rider, M. H. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.08.011 · Cited by 74 · see citing works
p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity
Baeza-Raja, B., Li, P., Le Moan, N., Sachs, B. D., Schachtrup, C., Davalos, D., Vagena, E., Bridges, D., Kim, C., Saltiel, A. R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103638109 · Cited by 53 · see citing works
Self-citationRegulation of cargo exocytosis by a Reps1-Ralbp1-RalA module
Wang, S., Chen, X., Crisman, L., Dou, X., Winborn, C. S., Wan, C., Puscher, H., Yin, Q., Kennedy, M. J., & Shen, J. (2023) · Science Advances · doi:10.1126/sciadv.ade2540 · Cited by 14 · see citing works
Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover
Feng, X., Zhang, S., Wang, Y., Kurlagunda, T., Sit, A., Jaishankar, P., Yang, P., Sakane, S., Park, S. Y., Wisessaowapak, C., et al. (2026) · Nature · doi:10.1038/s41586-026-10697-z · Cited by 2 · see citing works
Self-citation
- Authors
- Leto, D., & Saltiel, A. R.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Leto, Dara
- Saltiel, Alan R.
- ORCID
- Saltiel, Alan R.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2012-05-23
- Volume
- 13
- Issue
- 6
- Pages
- 383-396
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2132099317
- Cited by
- 848
- References
- 5
- Citations by year
- 2026: 43 · 2025: 61 · 2024: 66 · 2023: 57 · 2022: 66 · 2021: 70 · 2020: 58 · 2019: 62 · 2018: 66 · 2017: 68 · 2016: 49 · 2015: 69 · 2014: 50 · 2013: 51 · 2012: 11
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007315)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076906)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- GLUT4, insulin signaling, glucose transport, membrane trafficking, insulin resistance, type 2 diabetes, glucose homeostasis, insulin receptor, small GTPases, tethering complexes, vesicle fusion, GLUT4 storage vesicles, exocytosis, endosomal system, adipocytes, skeletal muscle
- MeSH terms
- Animals, Biological Transport, Endocytosis, Glucose, Humans, Insulin, Signal Transduction, Glucose Transporter Type 4
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