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Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Abstract
Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
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“This translocation results from stimulating p38 MAPK via either AMPK [10,44] or interaction with APPL1 [55].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [10]
In the citing paper
“Third, ApN induces the translocation of GLUT4 to the plasma membrane, thereby promoting glucose uptake [10,54].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [10]
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Shibata, S., Tada, Y., Asano, Y., Hau, C. S., Kato, T., Saeki, H., Yamauchi, T., Kubota, N., Kadowaki, T., & Sato, S. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101739 · Cited by 160
Adiponectin Receptors in Human Adipose Tissue: Effects of Obesity, Weight Loss, and Fat Depots
Rasmussen, M. S., Lihn, A. S., Pedersen, S. B., Bruun, J. M., Rasmussen, M., & Richelsen, B. (2006) · Obesity · doi:10.1038/oby.2006.5 · Cited by 164
Gable, D. R., Hurel, S. J., & Humphries, S. E. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.02.010 · Cited by 160
Nur77 Regulates Lipolysis in Skeletal Muscle Cells
Maxwell, M., Cleasby, M. E., Harding, A. S., Stark, A., Cooney, G. J., & Muscat, G. E. O. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409580200 · Cited by 159
Peterson, J. M., Aja, S. M., Wei, Z., & Wong, G. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.278333 · Cited by 158
Expression of Adiponectin Receptors and Its Possible Implication in the Human Endometrium
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Jaganathan, R., Ravindran, R., & Dhanasekaran, S. (2017) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2017.10.040 · Cited by 154
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Hao, Y., Zhu, Y., Zou, S., Zhou, P., Hu, Y., Zhao, Q., Gu, L., Zhang, H., Wang, Z., & Li, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.711060 · Cited by 165
“Adiponectin is an insulin sensitizer that ameliorates IR and regulates glucose and lipid metabolism by binding to its receptors, AdipoR1 and AdipoR2 (51).”
BackgroundInsulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?
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Adipocytokines and liver disease
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Adipolin/C1qdc2/CTRP12 Protein Functions as an Adipokine That Improves Glucose Metabolism
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Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?
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Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes
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Cross-talk between adipose tissue and vasculature: role of adiponectin
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“In contrast, adiponectin exerts anti-inflammatory actions [11] and enhances insulin sensitivity, counteracting the effect of TNF-α [12].”
Background
Metadata
- Authors
- Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., Murakami, K., Ohteki, T., Uchida, S., Takekawa, S., Waki, H., Tsuno, N. H., Shibata, Y., Terauchi, Y., Froguel, P., Tobe, K., Koyasu, S., Taira, K., Kitamura, T., Shimizu, T., Nagai, R., & Kadowaki, T.
- Affiliations
- The University of Tokyo (JP)
- Nissan Chemical Corporation (Japan) (JP)
- Japan Science and Technology Agency (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- Keio University (JP)
- Centre National de la Recherche Scientifique (FR)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Kadowaki, Takashi
- ORCID
- Venue
- Nature
- Published
- 2003-06-12
- Volume
- 423
- Issue
- 6941
- Pages
- 762-769
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1997978122
- Cited by
- 3,176
- References
- 28
- Citations by year
- 2026: 43 · 2025: 50 · 2024: 77 · 2023: 102 · 2022: 89 · 2021: 136 · 2020: 114 · 2019: 120 · 2018: 114 · 2017: 117 · 2016: 117 · 2015: 154 · 2014: 173 · 2013: 190 · 2012: 170
- FWCI
- 115.85
- Type
- journal article
- Language
- en
- Update notices
- erratum (2004-10-28)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Novartis Foundation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin, adiponectin receptors, AdipoR1, AdipoR2, insulin resistance, type 2 diabetes, AMP kinase, PPARα, fatty acid oxidation, glucose uptake, skeletal muscle, liver, adipokines, obesity, receptor cloning
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cloning, Molecular, Diabetes Mellitus, Endothelium, Vascular, Fatty Acids, Glucose, Humans, Hypoglycemic Agents, Ligands, Molecular Sequence Data, Oxidation-Reduction, Proteins, Receptors, Cell Surface, Transcription Factors, Receptors, Cytoplasmic and Nuclear, Hepatocytes, Muscle Cells, RNA Interference, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin, Receptors, Adiponectin
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