Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress.
Francesca UrbanoMarco BuglianiAgnese FilippelloAlessandra ScamporrinoStefania Di MauroAntonino Di PinoRoberto ScicaliDavide NotoAgata Maria RabuazzoMaurizio AvernaPiero MarchettiFrancesco PurrelloSalvatore PiroPublished in: Scientific reports (2017)
Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins.
Keyphrases
- oxidative stress
- induced apoptosis
- cardiovascular disease
- diabetic rats
- type diabetes
- dna damage
- ischemia reperfusion injury
- glycemic control
- endothelial cells
- single cell
- cell cycle arrest
- cell death
- coronary artery disease
- drug induced
- low density lipoprotein
- liquid chromatography
- electronic health record
- high glucose
- adipose tissue
- reactive oxygen species
- mass spectrometry
- emergency department
- combination therapy
- bone marrow
- metabolic syndrome
- heat shock
- big data
- human health
- weight loss