An important gene in the development of Type 2 diabetes mellitus

TXNIP- An important gene in the development of Type 2 diabetes mellitus

Thioredoxin interacting protein (TXNIP) is a gene that is powerfully suppressed by insulin yet is strongly stimulated by glucose intake. According to this study, TXNIP is consistently elevated in the muscles of prediabetics and diabetics. In this study, cultured adipocytes were forced to over-express TXNIP and this caused significantly lower glucose uptake. Also, using RNA interference, in adipocytes and skeletal muscle enhanced the ability of the cells to uptake glucose; therefore confirming that the gene product is also a glucose regulator.
Since TXNIP suppression is dependant on insulin (and regulates glucose uptake), this gene may have an important role in the regulation of fasting:feeding transitions. It is part of a negative feedback mechanism that prevents excess glucose uptake. TXNIP also has a role in β-cell toxicity. This study reported that TXNIP is glucose inducible in pancreatic β-cells and may mediate β-cell death through apoptosis. Insulin-deficiency or hyperglycemia can cause the increase in TXNIP, leading to β-cell death. In healthy individuals, the β-cells can compensate for this by increasing insulin production, but in diabetics β-cell compensation fails. This loss of β-cells can further exacerbate the problem as there is a reduce in insulin production, creating a vicious cycle.
Interventions aimed at modulating TXNIP activity may therefore help curtail this vicious cycle that eventually leads to overt Type 2 Diabetes Mellitus.

References:
Parikh H., Carlsson E., Chutkow W., et al (2007). "TXNIP Regulates Peripheral Glucose Metabolism in Humans." PLOS Medicine 4: 868-879.