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Metformin severely impairs in vivo muscle oxidative capacity in a rat model of type 2 diabetes
Ist Teil von
The FASEB journal, 2012-04, Vol.26 (S1)
Erscheinungsjahr
2012
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
Abstract only
Objective
To investigate the effects of metformin on
in vivo
and
in vitro
skeletal muscle mitochondrial function in Zucker diabetic fatty (ZDF) rats using
31
P magnetic resonance spectroscopy (MRS) and high‐resolution respirometry (HRR), respectively.
Methods
12‐week old healthy (
fa/+
) and diabetic (
fa/fa
) ZDF rats were treated with metformin (0, 30, 100 or 300 mg/kg body weight/day) for 15 days by oral gavage. At day 14,
in vivo
31
P MRS was performed on the
tibialis anterior
(TA) muscle to measure PCr recovery. At day 15, animals were killed and TA muscles were excised for
in vitro
HRR measurements.
Results
Metformin treatment decreased PCr recovery rates in a dose‐dependent manner in both healthy
fa/+
and diabetic
fa/fa
rats. Whereas, the clinical dose of 30 mg/kg/day had no significant effect, PCr recovery rates were ~22% and ~47% decreased at 100 and 300 mg/kg/day. HRR measurements showed a similar, but less pronounced effect of metformin on
in vitro
mitochondrial function.
Conclusion
Metformin treatment impairs
in vivo
skeletal muscle oxidative capacity in rats in a dose‐dependent manner.
This research was funded by a VIDI grant from the Netherlands Organisation for Scientific Research (NWO).