scholarly journals Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and Protracted Microvascular Retinopathy

2017 ◽  
Vol 58 (10) ◽  
pp. 3826 ◽  
Author(s):  
Woo Hyun Han ◽  
Jonathan Gotzmann ◽  
Sharee Kuny ◽  
Hui Huang ◽  
Catherine B. Chan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Respiration

scholarly journals Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

2009 ◽  
Vol 94 (4) ◽  
pp. 1372-1378 ◽  
Author(s):  
Rasmus Rabøl ◽  
Patricia M. V. Højberg ◽  
Thomas Almdal ◽  
Robert Boushel ◽  
Steen B. Haugaard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Respiration

Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes

2010 ◽  
Vol 12 (9) ◽  
pp. 806-814 ◽  
Author(s):  
R. Rabøl ◽  
R. Boushel ◽  
T. Almdal ◽  
C. N. Hansen ◽  
T. Ploug ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Respiration

scholarly journals Impaired Mitochondrial Respiration in Large Cerebral Arteries of Rats with Type 2 Diabetes

2017 ◽  
Vol 54 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Ivan Merdzo ◽  
Ibolya Rutkai ◽  
Venkata N.L.R. Sure ◽  
Catherine A. McNulty ◽  
Prasad V.G. Katakam ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Respiration ◽  
Cerebral Arteries

scholarly journals Inhibitory Effect of Metformin on Oxidation of NADH-Dependent Substrates in Rat Liver Homogenate

2011 ◽  
pp. 835-839 ◽  
Author(s):  
E. PÁLENÍČKOVÁ ◽  
M. CAHOVÁ ◽  
Z. DRAHOTA ◽  
L. KAZDOVÁ ◽  
M. KALOUS
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Liver Homogenate ◽  
Inhibitory Effect ◽  
Small Samples ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Wet Weight

Metformin is widely used in the treatment of Type 2 diabetes, however, mechanisms of its antihyperglycemic effect were not yet fully elucidated. Complex I of mitochondrial respiration chain is considered as one of the possible targets of metformin action. In this paper, we present data indicating that the inhibitory effect of metformin can be tested also in liver homogenate. Contrary to previous findings on hepatocytes or mitochondria under our experimental conditions, lower metformin concentrations and shorter time of preincubation give significant inhibitory effects. These conditions enable to study the mechanism of the inhibitory effect of metformin in small samples of biological material (50-100 mg wet weight) and compare more experimental groups of animals because isolation of mitochonria is unnecessary.

scholarly journals Regional Anatomic Differences in Skeletal Muscle Mitochondrial Respiration in Type 2 Diabetes and Obesity

2010 ◽  
Vol 95 (2) ◽  
pp. 857-863 ◽  
Author(s):  
R. Rabøl ◽  
S. Larsen ◽  
P. M. V. Højberg ◽  
T. Almdal ◽  
R. Boushel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Respiration ◽  
Diabetes And Obesity

scholarly journals Effects of prolonged type 2 diabetes on mitochondrial function in cerebral blood vessels

2019 ◽  
Vol 317 (5) ◽  
pp. H1086-H1092 ◽  
Author(s):  
Ivan Merdzo ◽  
Ibolya Rutkai ◽  
Venkata N. L. R. Sure ◽  
Prasad V. G. Katakam ◽  
David W. Busija
Keyword(s):  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Ros Production ◽  
Oxygen Species ◽  
Cerebral Blood Vessels

One of the major characteristics of hyperglycemic states such as type 2 diabetes is increased reactive oxygen species (ROS) generation. Since mitochondria are a major source of ROS, it is vital to understand the involvement of these organelles in the pathogenesis of ROS-mediated conditions. Therefore, we investigated mitochondrial function and ROS production in cerebral blood vessels of 21-wk-old Zucker diabetic fatty obese rats and their lean controls. We have previously shown that in the early stages of insulin resistance, and short periods of type 2 diabetes mellitus, only mild differences exist in mitochondrial function. In the present study, we examined mitochondrial respiration, mitochondrial protein expression, and ROS production in large-surface cerebral arteries. We used 21-wk-old animals exposed to peak glucose levels for 7 wk and compared them with our previous studies on younger diabetic animals. We found that the same segments of mitochondrial respiration (basal respiration and proton leak) were diminished in diabetic groups as they were in younger diabetic animals. Levels of rattin, a rat humanin analog, tended to decrease in the diabetic group but did not reach statistical significance ( P = 0.08). Other mitochondrial proteins were unaffected, which might indicate the existence of compensatory mechanisms with extension of this relatively mild form of diabetes. Superoxide levels were significantly higher in large cerebral vessels of diabetic animals compared with the control group. In conclusion, prolonged dietary diabetes leads to stabilization, rather than deterioration, of metabolic status in the cerebral circulation, despite continued overproduction of ROS. NEW & NOTEWORTHY We have characterized for the first time the dynamics of mitochondrial function during the progression of type 2 diabetes mellitus with regard to mitochondrial respiration, protein expression, and reactive oxygen species production. In addition, this is the first measurement of rattin levels in the cerebral vasculature, which could potentially lead to novel treatment options.

scholarly journals Endurance training remodels skeletal muscle phospholipid composition and increases intrinsic mitochondrial respiration in men with Type 2 diabetes

2019 ◽  
Vol 51 (11) ◽  
pp. 586-595 ◽  
Author(s):  
Maria F. Pino ◽  
Natalie A. Stephens ◽  
Alexey M. Eroshkin ◽  
Fanchao Yi ◽  
Andrew Hodges ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Phospholipid Composition ◽  
Rna Seq ◽  
Mitochondrial Dna Copy Number

The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised endurance training improves SKM mitochondrial function and insulin sensitivity that are related to alterations in lipid signatures within SKM of T2D (males n = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (RNA-Seq). From biopsies of SKM, tissue and primary myotubes mitochondrial respiration were quantified by high-resolution respirometry. We also performed hyperinsulinemic-euglycemic clamps and blood draws before and after the training. The lipidomics analysis revealed that endurance training (>95% compliance) increased monolysocardiolipin by 68.2% ( P ≤ 0.03), a putative marker of mitochondrial remodeling, and reduced total sphingomyelin by 44.8% ( P ≤ 0.05) and phosphatidylserine by 39.7% ( P ≤ 0.04) and tended to reduce ceramide lipid content by 19.8%. Endurance training also improved intrinsic mitochondrial respiration in SKM of T2D without alterations in mitochondrial DNA copy number or cardiolipin content. RNA-Seq revealed 71 transcripts in SKM of T2D that were differentially regulated. Insulin sensitivity was unaffected, and HbA1c levels moderately increased by 7.3% despite an improvement in cardiorespiratory fitness (V̇o2peak) following the training intervention. In summary, endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies lipid composition in men with T2D independently of alterations in insulin sensitivity and glycemic control.

Relationship Between Mitochondrial Respiration and Glucose Tolerance in Individuals at Risk of Type 2 Diabetes

2017 ◽  
Vol 49 (5S) ◽  
pp. 1021
Author(s):  
Justin J. Reid ◽  
Adam R. Konopka ◽  
William M. Castor ◽  
Jaime L. Laurin ◽  
Chistopher A. Wolff ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
At Risk ◽  
Glucose Tolerance ◽  
Mitochondrial Respiration

scholarly journals Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 324-337 ◽  
Author(s):  
Lisa M. Nicholas ◽  
Mototsugu Nagao ◽  
Laura C. Kusinski ◽  
Denise S. Fernandez-Twinn ◽  
Lena Eliasson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Mitochondrial Respiration ◽  
Caspase 3 ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Islet Function ◽  
Male And Female ◽  
The Impact

Abstract Aims/hypothesis Obesity during pregnancy increases offspring type 2 diabetes risk. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Whilst a number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function, it has not previously been delineated whether these changes are independent of other confounding risk factors such as obesity, postnatal high-fat-feeding and ageing. Thus, we aimed to study the impact of exposure to maternal obesity on offspring islets in young, glucose-tolerant male and female offspring. Methods Female C57BL/6J mice were fed ad libitum either chow or obesogenic diet prior to and throughout pregnancy and lactation. Offspring were weaned onto a chow diet and remained on this diet until the end of the study. An IPGTT was performed on male and female offspring at 7 weeks of age. At 8 weeks of age, pancreatic islets were isolated from offspring for measurement of insulin secretion and content, mitochondrial respiration, ATP content, reactive oxygen species levels, beta and alpha cell mass, granule and mitochondrial density (by transmission electron microscopy), and mRNA and protein expression by real-time RT-PCR and Western blotting, respectively. Results Glucose tolerance was similar irrespective of maternal diet and offspring sex. However, blood glucose was lower (p < 0.001) and plasma insulin higher (p < 0.05) in female offspring of obese dams 15 min after glucose administration. This was associated with higher glucose- (p < 0.01) and leucine/glutamine-stimulated (p < 0.05) insulin secretion in these offspring. Furthermore, there was increased mitochondrial respiration (p < 0.01) and density (p < 0.05) in female offspring of obese dams compared with same-sex controls. Expression of mitochondrial and nuclear-encoded components of the electron transport chain, L-type Ca2+ channel subtypes that play a key role in stimulus-secretion coupling [Cacna1d (p < 0.05)], and oestrogen receptor α (p < 0.05) was also increased in islets from these female offspring of obese dams. Moreover, cleaved caspase-3 expression and BAX:Bcl-2 were decreased (p < 0.05) reflecting reduced susceptibility to apoptosis. In contrast, in male offspring, glucose and leucine/glutamine-stimulated insulin secretion was comparable between treatment groups. There was, however, compromised mitochondrial respiration characterised by decreased ATP synthesis-driven respiration (p < 0.05) and increased uncoupled respiration (p < 0.01), reduced docked insulin granules (p < 0.001), decreased Cacna1c (p < 0.001) and Cacna1d (p < 0.001) and increased cleaved caspase-3 expression (p < 0.05). Conclusions/interpretation Maternal obesity programs sex differences in offspring islet function. Islets of female but not male offspring appear to be primed to cope with a nutritionally-rich postnatal environment, which may reflect differences in future type 2 diabetes risk.

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