AIM: Although metformin treatment has been reported to reduce the risk of cardiovascular events in patients with type 2 diabetes, the underlying mechanisms have not been elucidated fully. Here we assessed atherosclerotic lesion formation in newly established 2 mouse lines with different blood glucose levels (Oikawa-Nagao Diabetes-Prone [ON-DP] and -Resistant [ON-DR]) to evaluate the effect of metformin on early-stage atherosclerosis. METHODS: Mildly hyperglycemic ON-DP and normoglycemic ON-DR female mice fed an atherogenic diet for 20 weeks (8-28 weeks of age). During the feeding period, one group of each mouse line received metformin in drinking water (0.1%), while another group received water alone as control. Atherosclerotic lesion formation in the aortic sinus was quantitively analyzed from the oil red O-stained area of the serial sections. RESULTS: Metformin treatment did not affect food intake, body weight, and casual blood glucose levels within each mouse line during the 20-week feeding period. Nevertheless, metformin treatment significantly reduced atherosclerotic lesion formation in the ON-DP mice (59% of control), whereas no significant effect of metformin was observed in the lesion size of the ON-DR mice. CONCLUSION: Metformin can attenuate early-stage atherogenesis in mildly hyperglycemic ON-DP mice. Pleiotropic effects of metformin, beyond its glucose-lowering action, may contribute to the antiatherogenic property in the early-stage atherosclerosis.
AIM: Although metformin treatment has been reported to reduce the risk of cardiovascular events in patients with type 2 diabetes, the underlying mechanisms have not been elucidated fully. Here we assessed atherosclerotic lesion formation in newly established 2 mouse lines with different blood glucose levels (Oikawa-Nagao Diabetes-Prone [ON-DP] and -Resistant [ON-DR]) to evaluate the effect of metformin on early-stage atherosclerosis. METHODS: Mildly hyperglycemic ON-DP and normoglycemic ON-DR female mice fed an atherogenic diet for 20 weeks (8-28 weeks of age). During the feeding period, one group of each mouse line received metformin in drinking water (0.1%), while another group received water alone as control. Atherosclerotic lesion formation in the aortic sinus was quantitively analyzed from the oil red O-stained area of the serial sections. RESULTS:Metformin treatment did not affect food intake, body weight, and casual blood glucose levels within each mouse line during the 20-week feeding period. Nevertheless, metformin treatment significantly reduced atherosclerotic lesion formation in the ON-DPmice (59% of control), whereas no significant effect of metformin was observed in the lesion size of the ON-DR mice. CONCLUSION:Metformin can attenuate early-stage atherogenesis in mildly hyperglycemic ON-DPmice. Pleiotropic effects of metformin, beyond its glucose-lowering action, may contribute to the antiatherogenic property in the early-stage atherosclerosis.
Authors: A P Hall; C R Elcombe; J R Foster; T Harada; W Kaufmann; A Knippel; K Küttler; D E Malarkey; R R Maronpot; A Nishikawa; T Nolte; A Schulte; V Strauss; M J York Journal: Toxicol Pathol Date: 2012-06-21 Impact factor: 1.902
Authors: Hong Pei; Yinong Wang; Toru Miyoshi; Zhimin Zhang; Alan H Matsumoto; Gregory A Helm; George Tellides; Weibin Shi Journal: Circulation Date: 2006-11-13 Impact factor: 29.690
Authors: Alejandro Martin-Montalvo; Evi M Mercken; Sarah J Mitchell; Hector H Palacios; Patricia L Mote; Morten Scheibye-Knudsen; Ana P Gomes; Theresa M Ward; Robin K Minor; Marie-José Blouin; Matthias Schwab; Michael Pollak; Yongqing Zhang; Yinbing Yu; Kevin G Becker; Vilhelm A Bohr; Donald K Ingram; David A Sinclair; Norman S Wolf; Stephen R Spindler; Michel Bernier; Rafael de Cabo Journal: Nat Commun Date: 2013 Impact factor: 14.919