INT155234

Context Info Confidence 0.77 First Reported 2007 Last Reported 2010 Negated 0 Speculated 3 Reported most in Body Documents 48 Total Number 51 Disease Relevance 24.40 Pain Relevance 2.05

cytosol (TXNIP) nucleus (TXNIP) cell cycle (TXNIP) cytoplasm (TXNIP)

Anatomy Link Frequency muscle 12 adipocytes 3 skeletal muscle 2 fat 2 chondrocytes 1 TXNIP (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 64 99.12 Inflammation 13 99.00 tolerance 432 98.84 lidocaine 2 96.48 dexamethasone 48 76.20 cytokine 3 49.32 COX-2 inhibitor 3 29.04 anesthesia 48 5.00 alcohol 48 5.00 rheumatoid arthritis 3 5.00

Disease Link Frequency Relevance Heat Hyperglycemia 96 99.92 Diabetes Mellitus 2688 99.80 Obesity 816 99.52 Birth Weight 48 99.52 Prediabetic State 336 99.26 Osteoarthritis 71 99.12 Arteritis 2 99.00 Impaired Glucose Tolerance 384 98.84 Targeted Disruption 48 98.28 Disease 148 98.20

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Key novel results from the current study include the finding that TXNIP gene expression is reciprocally regulated by insulin and by glucose, that elevations in TXNIP can inhibit glucose uptake, and that TXNIP expression levels are consistently elevated in humans with T2DM and prediabetes.

Gene_expression (expression) of TXNIP associated with diabetes mellitus and prediabetic state

1) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.55 Pain Relevance 0

While TXNIP expression was also elevated in the muscle of Mexican Americans with T2DM (Figure 2B), we found no evidence of an elevation of TXNIP expression in the muscle of healthy Mexican Americans with a family history of T2DM (Figure 2B).

Gene_expression (expression) of TXNIP in muscle associated with diabetes mellitus

2) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.98 Pain Relevance 0.18

We found that TXNIP expression is inversely correlated with the total body rate of insulin-stimulated glucose metabolism in humans (Figure 4).

Gene_expression (expression) of TXNIP in body

3) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.41 Pain Relevance 0.08

Initially, the pancreas would compensate for this by producing more insulin, but this compensation would eventually fail, allowing blood sugar levels to rise sufficiently to increase TXNIP expression in the pancreas.

Gene_expression (expression) of TXNIP in pancreas

4) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Abstract Doc Link PMC1858708 Disease Relevance 0.53 Pain Relevance 0

Finally, by manipulating TXNIP expression levels in insulin-responsive cells grown in the laboratory, the researchers found that TXNIP overexpression reduced basal and insulin-stimulated glucose uptake but that reduced TXNIP expression had the opposite effect.

Gene_expression (overexpression) of TXNIP

5) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Abstract Doc Link PMC1858708 Disease Relevance 0.66 Pain Relevance 0

Finally, by manipulating TXNIP expression levels in insulin-responsive cells grown in the laboratory, the researchers found that TXNIP overexpression reduced basal and insulin-stimulated glucose uptake but that reduced TXNIP expression had the opposite effect.

Gene_expression (expression) of TXNIP

6) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Abstract Doc Link PMC1858708 Disease Relevance 0.68 Pain Relevance 0

TXNIP expression was suppressed by more than 1.5-fold (p < 0.003) after four hours of insulin treatment, clearly demonstrating that the suppression of TXNIP can occur in the absence of any changes in circulating glucose concentrations.

Gene_expression (expression) of TXNIP

7) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.22 Pain Relevance 0

We analyzed two previously published microarray datasets of human diabetic and control muscle [18,27] and found that TXNIP expression was elevated in northern Europeans with impaired glucose tolerance (IGT) or T2DM (Figure 2A).

Gene_expression (expression) of TXNIP in muscle associated with diabetes mellitus, tolerance and impaired glucose tolerance

8) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 1.01 Pain Relevance 0.17

Because TXNIP expression is suppressed by insulin signaling, it appears that TXNIP influences both insulin-dependent and insulin-independent arms of glucose uptake into cells.

Gene_expression (expression) of TXNIP in arms

9) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.64 Pain Relevance 0

Finally, by manipulating TXNIP expression levels in insulin-responsive cells grown in the laboratory, the researchers found that TXNIP overexpression reduced basal and insulin-stimulated glucose uptake but that reduced TXNIP expression had the opposite effect.

Gene_expression (expression) of TXNIP

10) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Abstract Doc Link PMC1858708 Disease Relevance 0.60 Pain Relevance 0

Txnip gene expression was more highly expressed (1.5-fold, p < 0.05) in the muscle of mice treated with streptozotocin, an agent that is selectively toxic to pancreatic ?

Gene_expression (expression) of Txnip gene in muscle

11) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.74 Pain Relevance 0.10

Together, these cell culture studies confirm that TXNIP expression is reciprocally regulated by insulin and glucose in human muscle and fat tissues.

Gene_expression (expression) of TXNIP in fat

12) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.07 Pain Relevance 0

end in 48 individuals, 23 of whom showed expression of TXNIP in muscle in the highest quartile, while 25 had TXNIP expression in lowest quartile from our previous studies [9,18].

Gene_expression (expression) of TXNIP in muscle

13) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.06 Pain Relevance 0

We hypothesized that the reciprocal regulation of TXNIP expression by insulin and glucose is likely mediated by highly conserved regulatory elements in the vicinity of its promoter (Figure S2).

Gene_expression (expression) of TXNIP

14) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.06 Pain Relevance 0

Txnip gene expression was more highly expressed (1.5-fold, p < 0.05) in the muscle of mice treated with streptozotocin, an agent that is selectively toxic to pancreatic ?

Gene_expression (expressed) of Txnip gene in muscle

15) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.74 Pain Relevance 0.10

They next used previously published microarray expression data to show that TXNIP expression was consistently higher in the muscles of patients with diabetes or prediabetes (a condition in which blood glucose levels are slightly raised) than in normal individuals.

Gene_expression (expression) of TXNIP in blood associated with diabetes mellitus and prediabetic state

16) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Abstract Doc Link PMC1858708 Disease Relevance 0.93 Pain Relevance 0

To exclude the possibility that the relationship between TXNIP expression and glucose uptake could be a consequence, rather than a cause, of the metabolic derangements that precede T2DM we also related the expression of skeletal muscle TXNIP to glucose uptake in 96 healthy, young, nondiabetic individuals (Methods, study C).

Gene_expression (expression) of TXNIP in skeletal muscle associated with diabetes mellitus

17) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.56 Pain Relevance 0.09

Key novel results from the current study include the finding that TXNIP gene expression is reciprocally regulated by insulin and by glucose, that elevations in TXNIP can inhibit glucose uptake, and that TXNIP expression levels are consistently elevated in humans with T2DM and prediabetes.

Gene_expression (expression) of TXNIP gene associated with diabetes mellitus and prediabetic state

18) Confidence 0.77 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.63 Pain Relevance 0

TXNIP expression increased following elevations in glucose concentration, and was suppressed by insulin (Figure 3).

Gene_expression (expression) of TXNIP

19) Confidence 0.67 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.13 Pain Relevance 0

To further confirm insulin's effect on TXNIP gene regulation, we analyzed TXNIP expression in cell culture.

Spec (analyzed) Gene_expression (expression) of TXNIP

20) Confidence 0.67 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1858708 Disease Relevance 0.24 Pain Relevance 0

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