| Title |
Lipids and immunoinflammatory pathways of beta cell destruction
|
|---|---|
| Published in |
Diabetologia, February 2016
|
| DOI | 10.1007/s00125-016-3890-y |
| Pubmed ID | |
| Authors |
Yumi Imai, Anca D. Dobrian, Margaret A. Morris, David A. Taylor-Fishwick, Jerry L. Nadler |
| Abstract |
Islet inflammation contributes to beta cell demise in both type 1 and type 2 diabetes. 12-Lipoxygenase (12-LO, gene expressed as ALOX12 in humans and 12-Lo in rodents in this manuscript) produces proinflammatory metabolites such as 12(S)-hydroxyeicosatetraenoic acids through dioxygenation of polyunsaturated fatty acids. 12-LO was first implicated in diabetes when the increase in 12-Lo expression and 12(S)-hydroxyeicosatetraenoic acid was noted in rodent models of diabetes. Subsequently, germline 12-Lo (-/-) was shown to prevent the development of hyperglycemia in mouse models of type 1 diabetes and in high-fat fed mice. More recently, beta cell-specific 12-Lo (-/-) was shown to protect mice against hyperglycaemia after streptozotocin and a high-fat diet. In humans, 12-LO expression is increased in pancreatic islets of autoantibody-positive, type 1 diabetic and type 2 diabetic organ donors. Interestingly, the high expression of ALOX12 is associated with the alteration in first-phase glucose-stimulated insulin secretion in human type 2 diabetic islets. To further clarify the role of islet 12-LO in diabetes and to validate 12-LO as a therapeutic target of diabetes, we have studied selective pharmacological inhibitors for 12-LO. The compounds we have identified show promise: they protect beta cell lines and human islets from apoptosis and preserve insulin secretion when challenged by proinflammatory cytokine mixture. Currently studies are underway to test the compounds in mouse models of diabetes. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied two other mini-reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x and Marc Donath, DOI: 10.1007/s00125-016-3873-z ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ). |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 2 | 50% |
| Canada | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Netherlands | 1 | 2% |
| Germany | 1 | 2% |
| Unknown | 41 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 20% |
| Student > Ph. D. Student | 6 | 14% |
| Student > Master | 5 | 11% |
| Student > Bachelor | 3 | 7% |
| Professor | 3 | 7% |
| Other | 9 | 20% |
| Unknown | 9 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 23% |
| Biochemistry, Genetics and Molecular Biology | 7 | 16% |
| Agricultural and Biological Sciences | 4 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 9% |
| Nursing and Health Professions | 2 | 5% |
| Other | 6 | 14% |
| Unknown | 11 | 25% |
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 April 2016.
All research outputs
#13,975,135
of 22,862,742 outputs
Outputs from Diabetologia
#4,281
of 5,036 outputs
Outputs of similar age
#203,931
of 400,611 outputs
Outputs of similar age from Diabetologia
#50
of 67 outputs
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