Abstract: Provided herein are methods, compounds, and compositions for reducing expression of phosphoenolpyruvate carboxykinase-mitochondrial (PEPCK-M) mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preventing or decreasing diabetes, obesity, metabolic syndrome, diabetic dyslipidemia, and/or hypertriglyceridemia in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of diabetes, obesity, metabolic syndrome, diabetic dyslipidemia, and/or hypertriglyceridemia, or a symptom thereof.

Abstract: Methods are provided for modulating CREB by administering a CREB-specific modulator. Also provided are methods for treating cardiovascular and metabolic disorders in a subject or delaying or preventing risk factors thereof through the modulation of CREB. The present invention is also directed to methods of decreasing lipid levels in a subject or for preventing or delaying the onset of a rise in lipid levels in a subject, comprising administering to said subject a CREB-specific inhibitor.