FOXO1 and type 2 diabetes mellitus: As an example, FoxO1 decreases glucose oxidation in the heart via promoting transcription of Pdk4, thereby increasing expression of PDH (pyruvate dehydrogenase) kinase 4, which phosphorylates and inactivates PDH, the rate-limiting enzyme of glucose oxidation.36 Moreover, pharmacological inhibition of FoxO1 fails to alleviate diastolic dysfunction in diabetic mice with a cardiac-specific deficiency of PDH,14 illustrating that increases in PDH activity and glucose oxidation contribute to how FoxO1 inhibition improves cardiac function in T2D.