294-LB: Transcriptome-Wide Signals Converge Upon Mitochondrial Function in Developmental Stages of Type 2 Diabetes in Human Skeletal Muscle

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 294-LB
Author(s):  
LUKASZ SZCZERBINSKI ◽  
MAGDALENA NIEMIRA ◽  
KAROL SZCZERBINSKI ◽  
URSZULA PUCHTA ◽  
ELWIRA SIEWIEC ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Human Skeletal Muscle ◽  
Developmental Stages

scholarly journals Skeletal muscle energetics are compromised only during high-intensity contractions in the Goto-Kakizaki rat model of type 2 diabetes

2019 ◽  
Vol 317 (2) ◽  
pp. R356-R368 ◽  
Author(s):  
Matthew T. Lewis ◽  
Jonathan D. Kasper ◽  
Jason N. Bazil ◽  
Jefferson C. Frisbee ◽  
Robert W. Wiseman
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Rat Model ◽  
Mitochondrial Function ◽  
The United States ◽  
Gk Rat ◽  
Muscle Energetics ◽  
Atp Production

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.

scholarly journals Physical Activity Is the Key Determinant of Skeletal Muscle Mitochondrial Function in Type 2 Diabetes

2012 ◽  
Vol 97 (9) ◽  
pp. 3261-3269 ◽  
Author(s):  
F. H. J. van Tienen ◽  
S. F. E. Praet ◽  
H. M. de Feyter ◽  
N. M. van den Broek ◽  
P. J. Lindsey ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Function

scholarly journals Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes

Diabetes ◽  
2002 ◽  
Vol 51 (10) ◽  
pp. 2944-2950 ◽  
Author(s):  
D. E. Kelley ◽  
J. He ◽  
E. V. Menshikova ◽  
V. B. Ritov
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle

scholarly journals Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

2003 ◽  
Vol 278 (12) ◽  
pp. 10436-10442 ◽  
Author(s):  
Kurt Højlund ◽  
Krzysztof Wrzesinski ◽  
Peter Mose Larsen ◽  
Stephen J. Fey ◽  
Peter Roepstorff ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Atp Synthase ◽  
Human Skeletal Muscle ◽  
Proteome Analysis ◽  
Β Subunit

scholarly journals Mitochondrial Function in Skeletal Muscle Is Normal and Unrelated to Insulin Action in Young Men Born with Low Birth Weight

2008 ◽  
Vol 93 (10) ◽  
pp. 3885-3892 ◽  
Author(s):  
Charlotte Brøns ◽  
Christine B. Jensen ◽  
Heidi Storgaard ◽  
Amra Alibegovic ◽  
Stine Jacobsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Young Men ◽  
Hepatic Insulin Resistance

Objective: Low birth weight (LBW) is an independent risk factor of insulin resistance and type 2 diabetes. Recent studies suggest that mitochondrial dysfunction and impaired expression of genes involved in oxidative phosphorylation (OXPHOS) may play a key role in the pathogenesis of insulin resistance in aging and type 2 diabetes. The aim of this study was to determine whether LBW in humans is associated with mitochondrial dysfunction in skeletal muscle. Methods: Mitochondrial capacity for ATP synthesis was assessed by 31phosphorus magnetic resonance spectroscopy in forearm and leg muscles in 20 young, lean men with LBW and 26 matched controls. On a separate day, a hyperinsulinemic euglycemic clamp with excision of muscle biopsies and dual-energy x-ray absorptiometry scanning was performed. Muscle gene expression of selected OXPHOS genes was determined by quantitative real-time PCR. Results: The LBW subjects displayed a variety of metabolic and prediabetic abnormalities, including elevated fasting blood glucose and plasma insulin levels, reduced insulin-stimulated glycolytic flux, and hepatic insulin resistance. Nevertheless, in vivo mitochondrial function was normal in LBW subjects, as was the expression of OXPHOS genes. Conclusions: These data support and expand previous findings of abnormal glucose metabolism in young men with LBW. In addition, we found that the young, healthy men with LBW exhibited hepatic insulin resistance. However, the study does not support the hypothesis that muscle mitochondrial dysfunction per se is the underlying key metabolic defect that explains or precedes whole body insulin resistance in LBW subjects at risk for developing type 2 diabetes.

scholarly journals Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle

Diabetologia ◽  
2007 ◽  
Vol 50 (4) ◽  
pp. 790-796 ◽  
Author(s):  
R. Boushel ◽  
E. Gnaiger ◽  
P. Schjerling ◽  
M. Skovbro ◽  
R. Kraunsøe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Function

scholarly journals The genetic regulatory signature of type 2 diabetes in human skeletal muscle

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura J. Scott ◽  
Michael R. Erdos ◽  
Jeroen R. Huyghe ◽  
Ryan P. Welch ◽  
Andrew T. Beck ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle
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