The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Soluble Insulin Receptor Ectodomain Is Elevated in the Plasma of Patients With Diabetes
Abstract
OBJECTIVE—Insulin binds to the α-subunit of the insulin receptor (IRα) and subsequently exerts its effects in the cells. The soluble ectodomains of several receptors have been found to circulate in the plasma. Therefore, we hypothesized that soluble human insulin receptor (hIR) ectodomain (α-subunit and a part of β-subunit) may exist in the plasma of diabetic patients. RESEARCH DESIGN AND METHODS—We identified soluble hIR ectodomain in human plasma by a two-step purification followed by immunoblotting and gel-filtration chromatography. Furthermore, we established an hIRα-specific enzyme-linked immunosorbent assay and measured the plasma IRα levels in patients with diabetes. We also investigated this phenomenon in streptozotocin-induced diabetic hIR transgenic mice. RESULTS—Soluble hIRα, but not intact hIRβ or whole hIR, exists in human plasma. The plasma IRα levels were significantly higher in type 1 (2.00 ± 0.60 ng/ml; n = 53) and type 2 (2.26 ± 0.80; n = 473) diabetic patients than in control subjects (1.59 ± 0.40 ng/ml; n = 123 (P < 0.001 vs. control). Plasma IRα level was positively correlated with blood glucose level, and 10–20% of the insulin in plasma bound to hIRα. In the in vivo experiments using diabetic hIR transgenic mice, hyperglycemia was confirmed to increase the plasma hIRα level and the half-life estimated to be ∼6 h. CONCLUSIONS—We propose that the increased soluble IR ectodomain level appears to be a more rapid glycemic marker than A1C or glycoalbumin.
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“Tissue expression of BACE1 and plasma levels of the IRsol are higher in patients with T2D, supporting the theory that BACE1 cleavage of IR drives the disease.”
From BACE1: More than just a β‐secretase (2022) · cites this paper as [87]
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Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
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Soluble receptors for cytokines and growth factors: generation and biological function
Rose-John, S., & Heinrich, P. C. (1994) · Biochemical Journal · doi:10.1042/bj3000281 · Cited by 775
Inoguchi, T., Battan, R., Handler, E., Sportsman, J. R., Heath, W., & King, G. L. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.11059 · Cited by 740
Izumi, Y. (1998) · The EMBO Journal · doi:10.1093/emboj/17.24.7260 · Cited by 521
Receptor-Mediated Transport of Insulin Across Endothelial Cells
King, G. L., & Johnson, S. M. (1985) · Science · doi:10.1126/science.3883490 · Cited by 471
Progression of diabetic nephropathy
Hovind, P., Rossing, P., Tarnow, L., Smidt, U. M., & Parving, H.-H. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.059002702.x · Cited by 383
Metalloprotease-Disintegrin MDC9: Intracellular Maturation and Catalytic Activity
Roghani, M., Becherer, J. D., Moss, M. L., Atherton, R. E., Erdjument-Bromage, H., Arribas, J., Blackburn, R. K., Weskamp, G., Tempst, P., & Blobel, C. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3531 · Cited by 319
Structure of the insulin receptor ectodomain reveals a folded-over conformation
McKern, N. M., Lawrence, M. C., Streltsov, V. A., Lou, M.-Z., Adams, T. E., Lovrecz, G. O., Elleman, T. C., Richards, K. M., Bentley, J. D., Pilling, P. A., et al. (2006) · Nature · doi:10.1038/nature05106 · Cited by 305
Ishii, H., Koya, D., & King, G. L. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050187 · Cited by 274
Jones, S. A., & Rose-John, S. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00319-1 · Cited by 255
Cited by
BACE1: More than just a β‐secretase
Taylor, H. A., Przemylska, L., Clavane, E. M., & Meakin, P. J. (2022) · Obesity Reviews · doi:10.1111/obr.13430 · Cited by 107
The beta secretase BACE1 regulates the expression of insulin receptor in the liver
Meakin, P. J., Mezzapesa, A., Benabou, E., Haas, M. E., Bonardo, B., Grino, M., Brunel, J.-M., Desbois-Mouthon, C., Biddinger, S. B., Govers, R., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03755-2 · Cited by 80
Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor
Guo, X., Asthana, P., Gurung, S., Zhang, S., Wong, S. K. K., Fallah, S., Chow, C. F. W., Che, S., Zhai, L., Wang, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31563-2 · Cited by 49
Preventing obesity, insulin resistance and type 2 diabetes by targeting MT1-MMP
Asthana, P., & Wong, H. L. X. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167081 · Cited by 13
Metadata
- Authors
- The Soluble Insulin Receptor Study Group
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-08-01
- Volume
- 56
- Issue
- 8
- Pages
- 2028-2035
- ISSN
- 0012-1797
- 1939-327X
- Cited by
- 38
- References
- 30
- Language
- en
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