Glucose homeostasis, the appropriate balancing of blood sugar levels, is impaired early in patients who become diabetic, causing life-threatening complications such as kidney failure and heart attacks. Studying the mechanisms of glucose homeostasis and early diabetes, Vamsi Mootha (Massachusetts General Hospital and Broad Institute), Leif Groop (University of Malmo) and colleagues have identified a key regulator of glucose homeostasis in humans. As they report in the international open-access medical journal PLoS Medicine, TXNIP is a gene whose expression is reciprocally regulated by insulin and glucose, TXNIP levels are consistently higher than normal in patients with type 2 diabetes and prediabetes, and such elevated levels can inhibit glucose uptake in muscle and fat cells. Mootha and colleagues propose that TXNIP normally regulates and integrates glucose uptake in the periphery of the human body by acting as a glucose- and insulin-sensitive switch, and that this function becomes compromised early the development of diabetes. Although many questions remain about the exact role of TXNIP in glucose homeostasis, the study's results help to explain many of the changes in glucose control that occur early in the development of diabetes. Furthermore, they suggest that interventions designed to modulate the activity of TXNIP might break the vicious cycle that eventually leads to type 2 diabetes. "TXNIP regulates peripheral glucose metabolism in humans" Parikh H, Carlsson E, Chutkow WA, Johansson LE, Storgaard H, et al. (2007) PLoS Med 4(5): e158.