Sex hormone binding globulin and insulin resistance
Abstract
Summary: Sex hormone binding globulin ( SHBG ) is a glycoprotein composed of two 373‐amino‐acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G ‐protein‐linked second‐messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus ( DM ) independent of sex hormone levels in men and women. Genetic studies using M endelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM . The correlation between SHBG and insulin resistance that is evident in a number of cross‐sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG ‐receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In PCOS compared with controls, SHBG has a strong inverse association with insulin resistance.
“Here, we report that in PCOS compared with controls SHBG had a strong inverse association with IR, confirming previous studies (Wallace et al., 2013).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Wallace et al., 2013
Most cross-sectional study results seem to support the hypothesis that IR initiates a reduction in HNF-4α that eventually leads to lower SHBG expression.
“However, most cross-sectional study results seem to support the hypothesis that IR initiates a reduction in HNF-4α that eventually leads to lower SHBG expression [132–134].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [132]
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6661 · Cited by 3,831 · see citing works
A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824 · see citing works
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342 · see citing works
NESTLER, J. E., POWERS, L. P., MATT, D. W., STEINGOLD, K. A., PLYMATE, S. R., RITTMASTER, R. S., CLORE, J. N., & BLACKARD, W. G. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-1-83 · Cited by 815 · see citing works
Pasquali, R., Gambineri, A., Biscotti, D., Vicennati, V., Gagliardi, L., Colitta, D., Fiorini, S., Cognigni, G. E., Filicori, M., & Morselli-Labate, A. M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6738 · Cited by 635 · see citing works
Oh, J.-Y., Barrett-Connor, E., Wedick, N. M., & Wingard, D. L. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.55 · Cited by 594 · see citing works
Diverse Roles for Sex Hormone-Binding Globulin in Reproduction
Hammond, G. L. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.092593 · Cited by 317 · see citing works
Miller, K. K., Rosner, W., Lee, H., Hier, J., Sesmilo, G., Schoenfeld, D., Neubauer, G., & Klibanski, A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030680 · Cited by 301 · see citing works
Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene
Selva, D. M., Hogeveen, K. N., Innis, S. M., & Hammond, G. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32249 · Cited by 232 · see citing works
Perry, J. R. B., Weedon, M. N., Langenberg, C., Jackson, A. U., Lyssenko, V., Sparsø, T., Thorleifsson, G., Grallert, H., Ferrucci, L., Maggio, M., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddp522 · Cited by 217 · see citing works
Vikan, T., Schirmer, H., Njølstad, I., & Svartberg, J. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0943 · Cited by 151 · see citing works
Sex Hormone-Binding Globulin as an Independent Predictor of Incident Type 2 Diabetes Mellitus in Men
Lakshman, K. M., Bhasin, S., & Araujo, A. B. (2010) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glq002 · Cited by 100 · see citing works
Shifren, J. L., Desindes, S., McIlwain, M., Doros, G., & Mazer, N. A. (2007) · Menopause · doi:10.1097/gme.0b013e31803867a · Cited by 89 · see citing works
de Lauzon-Guillain, B., Fournier, A., Fabre, A., Simon, N., Mesrine, S., Boutron-Ruault, M.-C., Balkau, B., & Clavel-Chapelon, F. (2009) · Diabetologia · doi:10.1007/s00125-009-1456-y · Cited by 86 · see citing works
Reinecke, H., Bogdanski, J., Woltering, A., Breithardt, G. Ü., Assmann, G., Kerber, S., & von Eckardstein, A. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02490-6 · Cited by 78 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cassar, S., Misso, M. L., Hopkins, W. G., Shaw, C. S., Teede, H. J., & Stepto, N. K. (2016) · Human Reproduction · doi:10.1093/humrep/dew243 · Cited by 415 · see citing works
Novel insights in SHBG regulation and clinical implications
Simó, R., Sáez-López, C., Barbosa-Desongles, A., Hernández, C., & Selva, D. M. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.05.001 · Cited by 335 · see citing works
Effects of a Ketogenic Diet in Overweight Women with Polycystic Ovary Syndrome
Paoli, A., Mancin, L., Giacona, M. C., Bianco, A., & Caprio, M. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02277-0 · Cited by 281 · see citing works
Narinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96 · see citing works
Effects of Mixed of a Ketogenic Diet in Overweight and Obese Women with Polycystic Ovary Syndrome
Cincione, R. I., Losavio, F., Ciolli, F., Valenzano, A., Cibelli, G., Messina, G., & Polito, R. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182312490 · Cited by 77 · see citing works
Gyawali, P., Martin, S. A., Heilbronn, L. K., Vincent, A. D., Jenkins, A. J., Januszewski, A. S., Taylor, A. W., Adams, R. J. T., O’Loughlin, P. D., & Wittert, G. A. (2018) · PLOS ONE · doi:10.1371/journal.pone.0200078 · Cited by 35 · see citing works
Dutta, S., Sengupta, P., Rao, S., Elgarawany, G. E., Samrot, A. V., Rosas, I. M., & Roychoudhury, S. (2025) · Pharmaceuticals · doi:10.3390/ph18101575 · Cited by 20 · see citing works
- Authors
- Wallace, I. R., McKinley, M. C., Bell, P. M., & Hunter, S. J.
- Affiliations
- Queen's University Belfast (GB)
- Royal Victoria Hospital (GB)
- Corresponding author
- Wallace, Ian R.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2013-01-25
- Volume
- 78
- Issue
- 3
- Pages
- 321-329
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2082413756
- Cited by
- 268
- References
- 16
- Citations by year
- 2026: 27 · 2025: 25 · 2024: 18 · 2023: 25 · 2022: 22 · 2021: 31 · 2020: 23 · 2019: 18 · 2018: 20 · 2017: 14 · 2016: 16 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Medical Research Council (MR/K023241/1)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- sex hormone-binding globulin, insulin resistance, type 2 diabetes, SHBG gene, single nucleotide polymorphisms, Mendelian randomization, G protein-coupled receptors, dietary factors, gene transcription
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Female, Humans, Insulin Resistance, Male, Sex Hormone-Binding Globulin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
