| Title |
Skeletal muscle insulin resistance is induced by 4-hydroxy-2-hexenal, a by-product of n-3 fatty acid peroxidation
|
|---|---|
| Published in |
Diabetologia, January 2018
|
| DOI | 10.1007/s00125-017-4528-4 |
| Pubmed ID | |
| Authors |
Christophe O. Soulage, Laura Sardón Puig, Laurent Soulère, Bader Zarrouki, Michel Guichardant, Michel Lagarde, Nicolas J. Pillon |
| Abstract |
Oxidative stress is involved in the pathophysiology of insulin resistance and its progression towards type 2 diabetes. The peroxidation of n-3 polyunsaturated fatty acids produces 4-hydroxy-2-hexenal (4-HHE), a lipid aldehyde with potent electrophilic properties able to interfere with many pathophysiological processes. The aim of the present study was to investigate the role of 4-HHE in the development of insulin resistance. 4-HHE concentration was measured in plasma from humans and rats by GC-MS. Insulin resistance was estimated in healthy rats after administration of 4-HHE using hyperinsulinaemic-euglycaemic clamps. In muscle cells, glucose uptake was measured using 2-deoxy-D-glucose and signalling pathways were investigated by western blotting. Intracellular glutathione was measured using a fluorimetric assay kit and boosted using 1,2-dithiole-3-thione (D3T). Circulating levels of 4-HHE in type 2 diabetic humans and a rat model of diabetes (obese Zucker diabetic fatty rats), were twice those in their non-diabetic counterparts (33 vs 14 nmol/l, p < 0.001), and positively correlated with blood glucose levels. During hyperinsulinaemic-euglycaemic clamps in rats, acute intravenous injection of 4-HHE significantly altered whole-body insulin sensitivity and decreased glucose infusion rate (24.2 vs 9.9 mg kg-1 min-1, p < 0.001). In vitro, 4-HHE impaired insulin-stimulated glucose uptake and signalling (protein kinase B/Akt and IRS1) in L6 muscle cells. Insulin-induced glucose uptake was reduced from 186 to 141.9 pmol mg-1 min-1 (p < 0.05). 4-HHE induced carbonylation of cell proteins and reduced glutathione concentration from 6.3 to 4.5 nmol/mg protein. Increasing intracellular glutathione pools using D3T prevented 4-HHE-induced carbonyl stress and insulin resistance. 4-HHE is produced in type 2 diabetic humans and Zucker diabetic fatty rats and blunts insulin action in skeletal muscle. 4-HHE therefore plays a causal role in the pathophysiology of type 2 diabetes and might constitute a potential therapeutic target to taper oxidative stress-induced insulin resistance. |
X Demographics
The data shown below were collected from the profiles of 42 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 5 | 12% |
| United States | 5 | 12% |
| Germany | 2 | 5% |
| France | 2 | 5% |
| Sweden | 2 | 5% |
| Myanmar | 1 | 2% |
| Mexico | 1 | 2% |
| Switzerland | 1 | 2% |
| Australia | 1 | 2% |
| Other | 4 | 10% |
| Unknown | 18 | 43% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 20 | 48% |
| Scientists | 14 | 33% |
| Practitioners (doctors, other healthcare professionals) | 8 | 19% |
Mendeley readers
The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 35 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 17% |
| Student > Master | 4 | 11% |
| Lecturer | 2 | 6% |
| Other | 2 | 6% |
| Student > Ph. D. Student | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 15 | 43% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Medicine and Dentistry | 3 | 9% |
| Chemistry | 2 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 4 | 11% |
| Unknown | 16 | 46% |
Attention Score in Context
This research output has an Altmetric Attention Score of 23. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2024.
All research outputs
#1,629,320
of 25,623,883 outputs
Outputs from Diabetologia
#866
of 5,366 outputs
Outputs of similar age
#36,525
of 451,963 outputs
Outputs of similar age from Diabetologia
#23
of 63 outputs
Altmetric has tracked 25,623,883 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
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