Thioredoxin interacting protein is a potential regulator of glucose and energy homeostasis in endogenous Cushing's syndrome.

Recent studies have described bone as an endocrine organ regulating glucose metabolism, with insulin signaling regulating osteocalcin secretion and osteocalcin regulating β cell function. We have previously demonstrated increased bone expression of TXNIP in patients with endogenous Cushing's syndrome (CS), and we hypothesized that TXNIP could contribute to the dysregulated glucose metabolism in CS. We studied 33 CS patients and 29 matched controls, with bone biopsies from nine patients, before and after surgical treatment. In vitro, the effect of silencing TXNIP (siTXNIP) in osteoblasts, including its effect on human islet cells, was examined. Our major findings were: (i) The high mRNA levels of TXNIP in bone from CS patients were significantly associated with high levels of glucose and insulin, increased insulin resistance, and decreased insulin sensitivity in these patients. (ii) Silencing TXNIP in osteoblasts enhanced their OC response to insulin and glucose and down-regulated interleukin (IL)-8 levels in these cells. (iii) Conditional media from siTXNIP-treated osteoblasts promoted insulin content and anti-inflammatory responses in human islet cells. We recently demonstrated that the thioredoxin/TXNIP axis may mediate some detrimental effects of glucocorticoid excess on bone tissue in CS. Here we show that alterations in this axis also may affect glucose metabolism in these patients

The Value of Macular Optical Coherence Tomography in Watchful Waiting of Suprasellar Masses: A 2-Year Observational Study

A possible benefit of optical coherence tomography (OCT) in the approach to tumors involving the optic chiasm may be the ability to foresee visual deterioration. This study investigated the value of OCT in watchful waiting for compressive optic neuropathy as the primary management of suprasellar masses

Silencing of TXNIP in hFOB.

<p>Gene expression of TXNIP (A) and OC (B) following 72 h silencing (24 h 33.5°C+48 h 39.5°C) using 25 nM siTXNIP (black columns) and 25 nM scrambled siSCR as control (white columns) in quadruplicate cultures before harvest. Cells were either treated with vehicle (US), glucose (5–25 mM) or insulin (2.5–100 nM), for 6 and 24 hours (TXNIP) and 24 hours (OC), in quadruplicate cultures before harvest. Gene expression of (C) INSR and (D) VKORC1 following 72 h silencing as described in A. mRNAs for TXNIP, OC, INSR and, VKORC1 were normalized to β-actin and expressed as relative mRNA levels. P-values represent one way ANOVA. (E) Protein levels of IL-8 in the supernatant following 72 h silencing as described in A. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064247#s3" target="_blank">Results</a> are presented as mean ± SEM; * <i>p</i><0.05, ** <i>p</i><0.01 and <i>p</i><0.001*** indicate difference between siSCR and siTXNIP treated cells.</p

TXNIP expression in nine paired bone biopsies pre and 3 months post surgery.

<p>(A) microarray analysis. B) mRNA expression normalized to β-actin and expressed as relative mRNA levels. (C) protein levels in three paired bone biopsies pre and 3 months post surgery and Ponceau S total protein staining by western blot and (D) protein levels in all the nine paired bone biopsies related to Ponceau S total protein staining.</p

Associations between the TRX/TXNIP axis and glucose metabolism <i>in vivo</i>.

<p>(A) Fasting glucose and insulin levels and indices of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) in 33 CS patients with active disease and 29 age-, sex- and BMI-matched controls. (B) Correlation between TXNIP mRNA expression in iliac crest bone biopsies from 7 CS patients with active disease and measures of glucose metabolism (due to shortage of serum from two of the patients). (C) Correlation between serum TRX levels and insulin resistance and insulin sensitivity in controls and CS patients with active disease.</p

Human islets treated with silenced TXNIP OB condition media showed increased function.

<p>Islets were treated with siTXNIP and siSCR OB medium for 24 h. (A) Insulin content normalized to DNA in cell extracts from six different donors (1–2 cultures per donor). (B–C) Gene expression for IL-1β and IL6 normalized to β-actin and expressed as relative mRNA levels.</p

Associations between OC and glucose metabolism <i>in vivo</i>.

<p>(A) Serum levels of ucOC in 33 CS patients with active disease and 29 age-, sex- and BMI-matched controls. (B) Correlation between serum levels of OC and indices of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) in controls and CS patients with active disease.</p