PTEN AND STATINS INDUCED NEW ONSET DIABETES


Yochai Birnbaum, M.D., Baylor College of Medicine, Houston, TX, USA

Background: High-dose statin therapy increases the incidence of new-onset diabetes. Studies in animal models have suggested that prolonged statin therapy upregulates Phosphatase and Tensin Homologue on Chromosome 10 (PTEN) expression. PTEN levels are also elevated in the heart, aorta and skeletal muscles of animals with diabetes, as well as the myocardium of diabetic patients. Increasing intracellular cAMP levels with subsequent activation of protein kinase A (PKA) decreases PTEN expression. We assessed whether prolonged treatment with high-dose statins induces diabetes and upregulates PTEN in the skeletal muscle of rats receiving Western Diet and whether concomitant treatment with cilostazol (CIL, a phosphodiesterase-3 inhibitor that increases cAMP levels) will attenuates the effects.

Methods: Rats received normal diet or Western diet without (control) or with rosuvastatin (ROS, 10 mg/kg/d), CIL (10 mg/kg/d), or ROS+CIL for 30 days.

Results: Western diet alone caused significant increase in glucose, GHbA1c and insulin. These levels were significantly higher in the ROS group. Western diet alone increased PTEN expression and decreased P-Akt levels. Levels of PTEN were significantly higher and P-Akt lower in the ROS than the control group. CIL normalized fasting glucose, GHbA1c and insulin levels and attenuated the changes in PTEN and P-Akt concentrations in the ROS+CIL group.

Conclusions: Long-term high dose statins can induce diabetes by upregulating PTEN that attenuates Akt activation. CIL attenuates these changes. Further studies are needed to assess the effects of increasing cAMP levels by GLP-1 activation or CIL to prevent induction of diabetes by statins.