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The glucocorticoid action has been implicated in the development of the Metabolic Syndrome.Systemic glucocorticoid excess induces central obesity,insulin resistance,dyslipidemia and hypertension,the same cluster of metabolic abnormalities in the Metabolic Syndrome.Although there is no convincing evidence of systemic glucocorticoid excess,the adipose-specific glucocorticoid production by 1 lbeta-HSD1 could be the cause of the Metabolic Syndrome.Therefore,1 lbeta-HSD1 inhibitors have potential therapies to improve insulin sensitivity in type 2 diabetes.Strategies to discover and improve 1 lbeta-HSD1 inhibitors will be discussed.