Sudip Bajpeyi1, Magdalena Pasarica2, Kevin E Conley3, Bradley R Newcomer4, Sharon A Jubrias3, Cecilia Gamboa5, Kori Murray6, Olga Sereda6, Lauren M Sparks7, Steven R Smith8. 1. Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA; Department of Kinesiology, University of Texas in El Paso, 500 University Ave, El Paso, TX 79968, USA. 2. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL 32804, USA. 3. Department of Radiology, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA 98195, USA. 4. Department of Clinical and Diagnostic Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. 5. Department of Kinesiology, University of Texas in El Paso, 500 University Ave, El Paso, TX 79968, USA. 6. Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. 7. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL 32804, USA; Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA. 8. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL 32804, USA; Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA. Electronic address: Steven.R.Smith.MD@flhosp.org.
Abstract
AIMS: Pioglitazone (Pio) is known to improve insulin sensitivity in skeletal muscle. However, the role of Pio in skeletal muscle lipid metabolism and skeletal muscle oxidative capacity is not clear. The aim of this study was to determine the effects of chronic Pio treatment on skeletal muscle mitochondrial activity in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS:Twenty-four participants with T2D (13M/11F 53.38±2.1years; BMI 36.47±1.1kg/m2) were randomized to either a placebo (CON, n=8) or a pioglitazone (PIO, n=16) group. Following 12weeks of treatment, we measured insulin sensitivity by hyperinsulinemic-euglycemic clamp (clamp), metabolic flexibility by calculating the change in respiratory quotient (ΔRQ) during the steady state of the clamp, intra- and extra-myocellular lipid content (IMCL and EMCL, respectively) by 1H magnetic resonance spectroscopy (1H-MRS) and muscle maximal ATP synthetic capacity (ATPmax) by 31P-MRS. RESULTS: Following 12weeks of PIO treatment, insulin sensitivity (p<0.0005 vs. baseline) and metabolic flexibility (p<0.05 vs. CON) significantly increased. PIO treatment significantly decreased IMCL content and increased EMCL content in gastrocnemius, soleus and tibialis anterior muscles. ATPmax was unaffected by PIO treatment. CONCLUSIONS: These results suggest that 12weeks of pioglitazone treatment improves insulin sensitivity, metabolic flexibility and myocellular lipid distribution without any effect on maximal ATP synthetic capacity in skeletal muscle. Consequently, pioglitazone-induced enhancements in insulin responsiveness and fuel utilization are independent of mitochondrial function.
RCT Entities:
AIMS: Pioglitazone (Pio) is known to improve insulin sensitivity in skeletal muscle. However, the role of Pio in skeletal muscle lipid metabolism and skeletal muscle oxidative capacity is not clear. The aim of this study was to determine the effects of chronic Pio treatment on skeletal muscle mitochondrial activity in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: Twenty-four participants with T2D (13M/11F 53.38±2.1years; BMI 36.47±1.1kg/m2) were randomized to either a placebo (CON, n=8) or a pioglitazone (PIO, n=16) group. Following 12weeks of treatment, we measured insulin sensitivity by hyperinsulinemic-euglycemic clamp (clamp), metabolic flexibility by calculating the change in respiratory quotient (ΔRQ) during the steady state of the clamp, intra- and extra-myocellular lipid content (IMCL and EMCL, respectively) by 1H magnetic resonance spectroscopy (1H-MRS) and muscle maximal ATP synthetic capacity (ATPmax) by 31P-MRS. RESULTS: Following 12weeks of PIO treatment, insulin sensitivity (p<0.0005 vs. baseline) and metabolic flexibility (p<0.05 vs. CON) significantly increased. PIO treatment significantly decreased IMCL content and increased EMCL content in gastrocnemius, soleus and tibialis anterior muscles. ATPmax was unaffected by PIO treatment. CONCLUSIONS: These results suggest that 12weeks of pioglitazone treatment improves insulin sensitivity, metabolic flexibility and myocellular lipid distribution without any effect on maximal ATP synthetic capacity in skeletal muscle. Consequently, pioglitazone-induced enhancements in insulin responsiveness and fuel utilization are independent of mitochondrial function.
Authors: Matthew T Lewis; Jonathan D Kasper; Jason N Bazil; Jefferson C Frisbee; Robert W Wiseman Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-06-12 Impact factor: 3.619
Authors: Manuel Amador; Cesar A Meza; Andrew J McAinch; George A King; Jeffrey D Covington; Sudip Bajpeyi Journal: Front Endocrinol (Lausanne) Date: 2020-03-13 Impact factor: 5.555