Unaltered Fatty Acid Uptake, Utilization, and Mitochondrial Respiration in Right Atrial Appendage of Type 2 Diabetic Human Heart

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 335-OR
Author(s):  
NANDINI RJ ◽  
SR RAJI ◽  
VIVEK V. PILLAI ◽  
JAYAKUMAR K. ◽  
SRINIVAS GOPALA
Heart ◽  
2015 ◽  
Vol 101 (Suppl 6) ◽  
pp. A1.2-A1
Author(s):  
MdL Sousa Fialho ◽  
LM Mansor ◽  
G Yea ◽  
RD Evans ◽  
WA Coumans ◽  
...  

Adipocyte ◽  
2015 ◽  
Vol 5 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Christophe Noll ◽  
Sébastien M. Labbé ◽  
Sandra Pinard ◽  
Michael Shum ◽  
Lyne Bilodeau ◽  
...  

2018 ◽  
Vol 20 (6) ◽  
pp. 1384-1390 ◽  
Author(s):  
Jukka Koffert ◽  
Mia Ståhle ◽  
Henry Karlsson ◽  
Patricia Iozzo ◽  
Paulina Salminen ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 150-OR
Author(s):  
ANNE-MARIE CARREAU ◽  
CHRISTOPHE NOLL ◽  
BRIGITTE GUERIN ◽  
LAURENT BIERTHO ◽  
ERIC E. TURCOTTE ◽  
...  

2003 ◽  
Vol 285 (2) ◽  
pp. E354-E362 ◽  
Author(s):  
Hubertina M. Wilmsen ◽  
Theodore P. Ciaraldi ◽  
Leslie Carter ◽  
Nabeela Reehman ◽  
Sunder R. Mudaliar ◽  
...  

We examined the regulation of free fatty acid (FFA, palmitate) uptake into skeletal muscle cells of nondiabetic and type 2 diabetic subjects. Palmitate uptake included a protein-mediated component that was inhibited by phloretin. The protein-mediated component of uptake in muscle cells from type 2 diabetic subjects (78 ± 13 nmol · mg protein-1 · min-1) was reduced compared with that in nondiabetic muscle (150 ± 17, P < 0.01). Acute insulin exposure caused a modest (16 ± 5%, P < 0.025) but significant increase in protein-mediated uptake in nondiabetic muscle. There was no significant insulin effect in diabetic muscle (+19 ± 19%, P = not significant). Chronic (4 day) treatment with a series of thiazolidinediones, troglitazone (Tgz), rosiglitazone (Rgz), and pioglitazone (Pio) increased FFA uptake. Only the phloretin-inhibitable component was increased by treatment, which normalized this activity in diabetic muscle cells. Under the same conditions, FFA oxidation was also increased by thiazolidinedione treatment. Increases in FFA uptake and oxidation were associated with upregulation of fatty acid translocase (FAT/CD36) expression. FAT/CD36 protein was increased by Tgz (90 ± 22% over control), Rgz (146 ± 42%), and Pio (111 ± 37%, P < 0.05 for all 3) treatment. Tgz treatment had no effect on fatty acid transporter protein-1 and membrane-associated plasmalemmal fatty acid-binding protein mRNA expression. We conclude that FFA uptake into cultured muscle cells is, in part, protein mediated and acutely insulin responsive. The basal activity of FFA uptake is impaired in type 2 diabetes. In addition, chronic thiazolidinedione treatment increased FFA uptake and oxidation into cultured human skeletal muscle cells in concert with upregulation of FAT/CD36 expression. Increased FFA uptake and oxidation may contribute to lower circulating FFA levels and reduced insulin resistance in skeletal muscle of individuals with type 2 diabetes following thiazolidinedione treatment.


Diabetes ◽  
2001 ◽  
Vol 50 (11) ◽  
pp. 2548-2554 ◽  
Author(s):  
M. Mensink ◽  
E. E. Blaak ◽  
M. A. van Baak ◽  
A. J.M. Wagenmakers ◽  
W. H.M. Saris

Diabetes ◽  
2011 ◽  
Vol 60 (2) ◽  
pp. 408-415 ◽  
Author(s):  
S. M. Labbe ◽  
E. Croteau ◽  
T. Grenier-Larouche ◽  
F. Frisch ◽  
R. Ouellet ◽  
...  

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Emmanuel Isaac ◽  
Stephanie Cooper ◽  
Matthew K Lancaster ◽  
Mahmoud loubani ◽  
Sandra A Jones

Background: Na v 1.5 is the predominantly expressed voltage-gated sodium channel (VGSC) isoform in the heart, responsible for phase 0 of the action potential. Our rodent studies have shown expression of neuronal isoform Na v 1.8 protein in the adult heart. Others have associated Na v 1.8 expression with aberrant sodium currents leading to increased frequency of arrhythmogenic episodes. Aim: To investigate age-associated changes in the protein expression of VGSCs Na v 1.5 and Na v 1.8 in the right atrial appendage of the human heart. Methods: Tissues from the right atrial appendage were obtained with NHS ethical approval (IRAS 197493) from patients undergoing routine cardiac surgery, coronary artery bypass or valve repair. The protein expression of VGSC isoforms Na v 1.5 and Na v 1.8 were quantified using specific protein-directed primary antibodies (Alomone, Israel) coupled with a secondary antibody conjugated to HRP for western blot (Abcam, UK), or Alexa Fluor 488 (ThermoFisher, UK) for immunohistochemistry with confocal microscopy (LSM 710 Zeiss, UK). Densities were quantified using Image J software. Results: Derived from 26 patients, the protein expression of Na v 1.5 arranged in chronological age order (43-87 years of age) demonstrated a negative correlation between increasing age and Na v 1.5 protein expression (Pearson correlation coefficient of -0.25). The contrary was shown for Na v 1.8, which had a positive correlation with increasing age (Pearson correlation coefficient of 0.26), as older patients show increased Na v 1.8 protein expression. This novel finding was reflected when we compared confocal images from elderly patients with their younger counterparts, as the elderly showed a higher density of labelled Na v 1.8 protein and a lower density of labelled Na v 1.5 protein, particularly located at the t-tubules and intercalated disks. Conclusion: With increasing chronological age, the human heart reduces expression of the predominant cardiac isoform Na v 1.5 whilst increasing the expression of Na v 1.8: This finding has the potential to increase the risk of an elderly person’s heart to an increased susceptibility of arrhythmias.


2017 ◽  
Vol 313 (2) ◽  
pp. E175-E182 ◽  
Author(s):  
Prince Dadson ◽  
Ele Ferrannini ◽  
Linda Landini ◽  
Jarna C. Hannukainen ◽  
Kari K. Kalliokoski ◽  
...  

Body fat accumulation, distribution, and metabolic activity are factors in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated adipose blood flow, fatty acid uptake (FAU), and subcutaneous and visceral fat cellularity in obese patients with or without T2D. A total of 23 morbidly obese (mean body mass index = 42 kg/m2) patients were studied before and 6 mo after bariatric surgery; 15 nonobese subjects served as controls. Positron emission tomography was used to measure tissue FAU (with 18F-FTHA) and blood flow (with H215O); MRI was used for fat distribution and fat biopsy for adipocyte size. Obese subjects had subcutaneous hyperplasia and hypertrophy and lower blood flow; when expressed per cell, flow was similar to controls. FAU into subcutaneous and visceral depots was increased in the obese; per unit tissue mass, however, FAU was similar to controls but reduced in skeletal muscle. Fatty acid fractional extraction in subcutaneous fat and muscle was only increased in obese patients with T2D. We conclude that surgery reduces subcutaneous fat hyperplasia and hypertrophy; subcutaneous blood flow and FAU decrease in absolute terms and per cell while fractional FAU remains unchanged in T2D. In the obese, subcutaneous blood flow is a determinant of FAU and is coupled with cellularity; efficiency of FAU is enhanced in subcutaneous fat and muscle in T2D.


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