Obesity-associated diabetes, and concomitant inflammation may compromise pancreatic β-cell integrity and function. L-glutamine and L-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. Here we studied whether the dipeptide L-Alanyl-L-Glutamine (Ala-Gln) could exert protective effects via Sirtuin 1/Hur (SIRT1/HUR) signalling in β-cells, against detrimental responses following ex vivo stimulation with inflammatory mediators-derived from macrophages (IMM). The macrophages were derived from blood obtained from obese individuals. Macrophages were exposed (or not) to Lipopolysaccharide (LPS) to generate a pro-inflammatory cytokine cocktail. The cytokine profile was determined following analysis by flow cytometry. Insulin secreting BRIN-BD11 β-cells were exposed to IMM and then cultured with or without Ala-Gln for 24 h. Chronic insulin secretion, L-glutamine-glutathione (GSH) axis, and the level of insulin receptor β (IRβ), Heat shock protein 70 (HSP70), SIRT1/HUR, CCAAT-enhancer-binding protein homologous protein (CHOP) and Cytochrome c Oxidase IV (COX IV) were evaluated. Cytokine concentrations, including IL-1β, IL-6, IL-10 and TNF-α in the IMM was higher following exposure to LPS. Subsequently, when β-cells were exposed to IMM, chronic insulin secretion, IRβ and COX IV levels were decreased, but these effects were partially or fully attenuated by the addition of Ala-Gln. The glutamine-GSH axis and HSP70 levels, which were compromised by IMM, were also restored by Ala-Gln, possibly due to protection of of SIRT1/HUR levels, and a reduction of CHOP expression. Using an ex vivo inflammatory approach, we have demonstrated Ala-Gln dependent β-cell protection mediated by coordinated effects on glutamine-GSH axis, and HSP pathway, maintenance of mitochondrial metabolism and stimulus-secretion coupling essential for insulin release.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Immunology and Microbiology
2
6%
Sports and Recreations
2
6%
Other
5
14%
Unknown
8
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 20 October 2016.
All research outputs
#16,046,765
of 25,371,288 outputs
Outputs from Journal of Endocrinology
#1,887
of 2,527 outputs
Outputs of similar age
#199,201
of 359,527 outputs
Outputs of similar age from Journal of Endocrinology
#7
of 14 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,527 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 359,527 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
