Monday, January 11, 2010

TXNIP - lots of data

A new report by Zhou, et al. (Nature Immunolog, links thioredoxin (TRX)-interacting protein (TXNIP) to oxidative stress and inflammation. This gene has been connected to insulin resistance and a host of other activities. These include:

mouse knockouts show increased fat to muscle ratio

TXNIP is a rat hyperlipidemia gene (rat genome database)

highly expressed in mouse adipose (3.23-fold over average of all other tissues)

TXNIP expression was inversely correlated to total body measures of glucose uptake (Parikh, Mootha 2007 PLos Med)

forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming a role as a regulator of glucose uptake (Parikh, Mootha 2007 PLos Med)

TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM (Parikh, Mootha 2007 PLos Med)

TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle (Parikh, Mootha 2007 PLos Med)

this is gene #135 in a published PPARA signaling network analysis (Cavalieri, Muller 2009 BMC Genomics 10:596)

TXNIP is 1.5-fold increased expression in young vs. old mouse skeletal muscle. In old muscle, calorie restriction turns up the gene (young phenotype) also ~1.5-fold over normal diet (GDS2612)

So, perhaps the newest paper is not surprising, but welcome data to integrate into the big picture.

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