Abstract: The present invention provides methods for determining a putative agent that treats or prevents obesity and/or diabetes or increasing insulin sensitivity, the method comprising contacting cells with the putative agent and measuring thioredoxin-interacting protein (TXNIP) or thioredoxin expression or activity in the cells. The present invention also provides the agent, the pharmaceutical composition, and methods of preventing or treating obesity and/or diabetes or of increasing insulin sensitivity or glucose sensitivity, the method comprising administration of the agent that decreases the expression of TXNIP or activity of TXNIP.