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[PMID]: | 28452488 |
[Au] Autor: | Garcia-Contreras M; Tamayo-Garcia A; Pappan KL; Michelotti GA; Stabler CL; Ricordi C; Buchwald P |
[Ad] Endereço: | Diabetes Research Institute, Miller School of Medicine, University of Miami , Miami, Florida 33136, United States. |
[Ti] Título: | Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on Isolated Human Pancreatic Islets. |
[So] Source: | J Proteome Res;16(6):2294-2306, 2017 Jun 02. | [Is] ISSN: | 1535-3907 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation. Metabolomics profiling of media and cell samples identified a total of 241 and 361 biochemicals, respectively. Metabolites that were altered in highly significant manner in both included, for example, kynurenine, kynurenate, citrulline, and mannitol/sorbitol under inflammation (all elevated) plus lactate (elevated) and N-formylmethionine (depressed) for hypoxia. Dynamic GSIR experiments, which capture both first- and second-phase insulin release, found severely depressed insulin-secretion under hypoxia, whereas elevated baseline and stimulated insulin-secretion was measured for islet exposed to the inflammatory cytokine cocktail (IL-1ß, IFN-γ, and TNF-α). Because of the uniquely large changes observed in kynurenine and kynurenate, they might serve as potential biomarkers of islet inflammation, and indoleamine-2,3-dioxygenase on the corresponding pathway could be a worthwhile therapeutic target to dampen inflammatory effects. |
[Mh] Termos MeSH primário: |
Hiperglicemia Hipóxia Inflamação Ilhotas Pancreáticas/metabolismo Metabolômica/métodos
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[Mh] Termos MeSH secundário: |
Biomarcadores/análise Seres Humanos Inflamação/diagnóstico Insulina/secreção Transplante das Ilhotas Pancreáticas Ácido Cinurênico/análise Cinurenina/análise
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Biomarkers); 0 (Insulin); 343-65-7 (Kynurenine); H030S2S85J (Kynurenic Acid) |
[Em] Mês de entrada: | 1803 |
[Cu] Atualização por classe: | 180309 |
[Lr] Data última revisão:
| 180309 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170429 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1021/acs.jproteome.7b00160 |
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