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.

Mitochondrial oxidative function and type 2 diabetes

2006 ◽  
Vol 31 (6) ◽  
pp. 675-683 ◽  
Author(s):  
Rasmus Rabøl ◽  
Robert Boushel ◽  
Flemming Dela
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Electron Transport ◽  
Mitochondrial Function ◽  
Oxidative Enzymes ◽  
Mitochondrial Content ◽  
Atp Production ◽  
Oxidative Function

The cause of insulin resistance and type 2 diabetes is unknown. The major part of insulin-mediated glucose disposal takes place in the skeletal muscle, and increased amounts of intramyocellular lipid has been associated with insulin resistance and linked to decreased activity of mitochondrial oxidative phosphorylation. This review will cover the present knowledge and literature on the topics of the activity of oxidative enzymes and the electron transport chain (ETC) in skeletal muscle of patients with type 2 diabetes. Different methods of studying mitochondrial function are described, including biochemical measurements of oxidative enzyme and electron transport activity, isolation of mitochondria for measurements of respiration, and ATP production and indirect measurements of ATP production using nuclear magnetic resonance (NMR) - spectroscopy. Biochemical markers of mitochondrial content are also discussed. Several studies show reduced activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The reductions are independent of muscle fiber type, and are accompanied by visual evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme activity is explained by decreases in mitochondrial content; thus, evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing. These impairments in oxidative function and mitochondrial morphology could reflect the sedentary lifestyle of the diabetic subjects, and the influence of physical activity on oxidative activity and mitochondrial function is discussed. The studies on insulin-resistant offspring of type 2 diabetic parents have provided important insights in the earliest metabolic defects in type 2 diabetes. These defects include reductions in basal ATP production and an attenuated response to insulin stimulation. The decreased basal ATP production does not affect overall lipid or glucose oxidation, and no studies linking changes in oxidative activity and insulin sensitivity in type 2 diabetes have been published. It is concluded that evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing, and that intervention studies describing the correlation between changes in insulin resistance and mitochondrial function in type 2 diabetes are lacking. Specific effects of regular physical training and muscular work on mitochondrial function and plasticity in type 2 diabetes remain an important area of research.

scholarly journals Skeletal Muscle Mitochondrial Function in Goto‐Kakizaki Rat Model of Type 2 Diabetes

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Matthew T Lewis ◽  
Jonathan D Kasper ◽  
Jason N Bazil ◽  
Jefferson C Frisbee ◽  
Ronald A Meyer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Rat Model ◽  
Mitochondrial Function

scholarly journals Proanthocyanidins Ameliorated Deficits of Lipid Metabolism in Type 2 Diabetes Mellitus Via Inhibiting Adipogenesis and Improving Mitochondrial Function

2020 ◽  
Vol 21 (6) ◽  
pp. 2029
Author(s):  
Fangfang Tie ◽  
Jifei Wang ◽  
Yuexin Liang ◽  
Shujun Zhu ◽  
Zhenhua Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Mitochondrial Function ◽  
Underlying Mechanism ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Mass

Proanthocyanidins are the major active compounds extracted from Iris lactea Pall. var. Chinensis (Fisch.) Koidz (I. lactea). Proanthocyanidins exhibit a variety of pharmacological activities such as anti-oxidation, anti-inflammation, anti-tumor, and lowering blood lipids. However, the underlying mechanism of its regulating effect on lipid metabolism in diabetic conditions remains unclear. The present study investigated the effects of I. lactea-derived proanthocyanidins on lipid metabolism in mice of type 2 diabetes mellitus (T2DM). Results demonstrated a beneficial effect of total proanthocyanidins on dysregulated lipid metabolism and hepatic steatosis in high-fat-diet/streptozocin (STZ)-induced T2DM. To identify the mechanisms, six flavan-3-ols were isolated from proanthocyanidins of I. lacteal and their effects on adipogenesis and dexamethasone (Dex)-induced mitochondrial dysfunctions in 3T3-L1 adipocytes were determined. In vitro studies showed flavan-3-ols inhibited adipogenesis and restored mitochondrial function after Dex-induced insulin resistance, being suggested by increased mitochondrial membrane potential, intracellular ATP contents, mitochondrial mass and mitochondrial biogenesis, and reduced reactive oxygen species. Among the six flavan-3-ols, procyanidin B3 and procyanidin B1 exhibited the strongest effects. Our study suggests potential of proanthocyanidins as therapeutic target for diabetes.

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 Fetal Insulin-Like Growth Factor-2 Production Is Impaired in the GK Rat Model of Type 2 Diabetes

Diabetes ◽  
2002 ◽  
Vol 51 (2) ◽  
pp. 392-397 ◽  
Author(s):  
P. Serradas ◽  
L. Goya ◽  
M. Lacorne ◽  
M.-N. Gangnerau ◽  
S. Ramos ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Rat Model ◽  
Insulin Like Growth Factor ◽  
Gk Rat

Early development of beta-cells is impaired in the GK rat model of type 2 diabetes

Diabetes ◽  
2001 ◽  
Vol 50 (Supplement 1) ◽  
pp. S84-S88 ◽  
Author(s):  
F. Miralles ◽  
B. Portha
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cells ◽  
Early Development ◽  
Rat Model ◽  
Gk Rat

scholarly journals EGb761, a Ginkgo Biloba Extract, Is Effective Against Atherosclerosis In Vitro, and in a Rat Model of Type 2 Diabetes

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20301 ◽  
Author(s):  
Soo Lim ◽  
Ji Won Yoon ◽  
Seon Mee Kang ◽  
Sung Hee Choi ◽  
Bong Jun Cho ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract

scholarly journals Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

2020 ◽  
Vol 21 (14) ◽  
pp. 5045
Author(s):  
Istvan Kovanecz ◽  
Robert Gelfand ◽  
Sheila Sharifzad ◽  
Alec Ohanian ◽  
William DeCastro ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Incontinence ◽  
Stem Cell ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Male Rats ◽  
Female Stress Urinary Incontinence ◽  
Female Rat

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.

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