Sex hormone binding globulin and insulin resistance

Abstract

SummarySex 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 Mendelian 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.

Testosterone and glucose metabolism in men: current concepts and controversies

“…In addition, testosterone therapy decreases SHBG. SHBG may have biological actions that improve glucose metabolism (Wallace et al 2013). Future studies should clarify whether effects of testosterone on adiponectin, SHBG and other potential regulators of glucose metabolism, such as undercarboxylated osteocalcin (Yeap 2011), may limit testosterone therapy-mediated improvements in glucose metabolism.…”

“…This is because of the confounding effects of SHBG, itself being a strong associate of insulin resistance (Wallace et al 2013). In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident metabolic syndrome (Bhasin et al 2011a).…”

“…In cross-sectional studies of men with (Grossmann et al 2008) and without (Bonnet et al 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control. SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids (Wallace et al 2013). However, this is yet unproven.…”

PCOS and diabetes mellitus: from insulin resistance to altered beta pancreatic function, a link in evolution

“…This can be added up to the adverse action caused by the increase of body mass index, as previously stated [1]. Several researches have proved a negative correlation between SHBG levels and insulin sensitivity [5]. In addition, most prospective studies support the role of reduced SHBG levels as a possible predictive factor of DM2 development [6].…”

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS

“…SHBG is a protective factor, and a low level of SHBG might serve as a critical factor during the pathogenesis of PCOS and MetS [27]. Several sources of evidence have shown that decreased SHBG is associated with MetS and IR in women with PCOS [28][29][30][31][32]. Therefore, paternal history aggravates the metabolic disturbance in PCOS patients.…”