Lewis 2019 Am J Physiol Regul Integr Comp Physiol

Lewis MT, Kasper JD, Bazil JN, Frisbee JC, Wiseman RW (2019) Skeletal muscle energetics are compromised only during high-intensity contractions in the Goto-Kakizaki rat model of type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 317:R356-68.

» PMID: 31188651

Lewis MT, Kasper JD, Bazil JN, Frisbee JC, Wiseman RW (2019) Am J Physiol Regul Integr Comp Physiol

Abstract: Type 2 diabetes (T2D) presents with hyperglycemia and insulin resistance, affecting over 30 million people in the United States alone. Previous work has hypothesized that mitochondria are dysfunctional in T2D and results in both reduced ATP production and glucose disposal. However, a direct link between mitochondrial function and T2D has not been determined. In the current study, the Goto-Kakizaki (GK) rat model of T2D was used to quantify mitochondrial function in vitro and in vivo over a broad range of contraction-induced metabolic workloads. During high-frequency sciatic nerve stimulation, hindlimb muscle contractions at 2- and 4-Hz intensities, the GK rat failed to maintain similar bioenergetic steady states to Wistar control (WC) rats measured by phosphorus magnetic resonance spectroscopy, despite similar force production. Differences were not due to changes in mitochondrial content in red (RG) or white gastrocnemius (WG) muscles (cytochrome c oxidase, RG: 22.2 ± 1.6 vs. 23.3 ± 1.7 U/g wet wt; WG: 10.8 ± 1.1 vs. 12.1 ± 0.9 U/g wet wt; GK vs. WC, respectively). Mitochondria isolated from muscles of GK and WC rats also showed no difference in mitochondrial ATP production capacity in vitro, measured by high-resolution respirometry. At lower intensities (0.25-1 Hz) there were no detectable differences between GK and WC rats in sustained energy balance. There were similar phosphocreatine concentrations during steady-state contraction and postcontractile recovery (τ = 72 ± 6 s GK versus 71 ± 2 s WC). Taken together, these results suggest that deficiencies in skeletal muscle energetics seen at higher intensities are not due to mitochondrial dysfunction in the GK rat. • Keywords: Hyperglycemia, Inactivity, Insulin resistance, Mitochondrial oxidative phosphorylation, Obesity • Bioblast editor: Plangger M • O2k-Network Lab: US MI East Lansing Bazil JN

Labels: MiParea: Respiration  Pathology: Diabetes 

Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 

Regulation: PCr;Cr  Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k 

2020-04