| Title |
Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo
|
|---|---|
| Published in |
Metabolomics, April 2016
|
| DOI | 10.1007/s11306-016-1022-9 |
| Pubmed ID | |
| Authors |
Amro Ilaiwy, Miao Liu, Traci L. Parry, James R. Bain, Christopher B. Newgard, Jonathan C. Schisler, Michael J. Muehlbauer, Florin Despa, Monte S. Willis |
| Abstract |
Chronic hypersecretion of the 37 amino acid amylin is common in type 2 diabetics (T2D). Recent studies implicate human amylin aggregates cause proteotoxicity (cell death induced by misfolded proteins) in both the brain and the heart. Identify systemic mechanisms/markers by which human amylin associated with cardiac and brain defects might be identified. We investigated the metabolic consequences of amyloidogenic and cytotoxic amylin oligomers in heart, brain, liver, and plasma using non-targeted metabolomics analysis in a rat model expressing pancreatic human amylin (HIP model). Four metabolites were significantly different in 3 or more of the the four compartments (heart, brain, liver, and plasma) in HIP rats. When compared to a T2D rat model, HIP hearts uniquely had significant DECREASES in five amino acids (lysine, alanine, tyrosine, phenylalanine, serine), with phenylalanine decreased across all four tissues investigated, including plasma. In contrast, significantly INCREASED circulating phenylalanine is reported in diabetics in multiple recent studies. DECREASED phenylalanine may serve as a unique marker of cardiac and brain dysfunction due to hyperamylinemia that can be differentiated from alterations in T2D in the plasma. While the deficiency in phenylalanine was seen across tissues including plasma and could be monitored, reduced tyrosine was seen only in the brain. The 50% reduction in phenylalanine and tyrosine in HIP brains is significant given their role in supporting brain chemistry as a precursor for catecholamines (dopamine, norepinephrine, epinephrine), which may contribute to the increased morbidity and mortality in diabetics at a multi-system level beyond the effects on glucose metabolism. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 23% |
| Student > Postgraduate | 3 | 12% |
| Student > Bachelor | 2 | 8% |
| Other | 2 | 8% |
| Researcher | 2 | 8% |
| Other | 4 | 15% |
| Unknown | 7 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 23% |
| Biochemistry, Genetics and Molecular Biology | 3 | 12% |
| Nursing and Health Professions | 2 | 8% |
| Business, Management and Accounting | 1 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Other | 4 | 15% |
| Unknown | 9 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 23 April 2016.
All research outputs
#18,453,763
of 22,865,319 outputs
Outputs from Metabolomics
#1,072
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Outputs of similar age
#219,046
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Outputs of similar age from Metabolomics
#27
of 33 outputs
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