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Open AccessArticle

Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes

1
Diabetes Research Institute and Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27708, USA
3
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
4
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
5
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
6
Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(10), 207; https://doi.org/10.3390/metabo9100207
Received: 28 August 2019 / Revised: 26 September 2019 / Accepted: 27 September 2019 / Published: 29 September 2019
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of “localized metabolomics” where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection. View Full-Text
Keywords: autoimmune diabetes; anterior chamber of the eye; gender differences; non-obese diabetic (NOD) mice; pancreatic islet; local metabolomics; non-targeted metabolomics; GC-MS; islet microenvironment; T1D biomarkers autoimmune diabetes; anterior chamber of the eye; gender differences; non-obese diabetic (NOD) mice; pancreatic islet; local metabolomics; non-targeted metabolomics; GC-MS; islet microenvironment; T1D biomarkers
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MDPI and ACS Style

Alcazar, O.; Hernandez, L.F.; Tschiggfrie, A.; Muehlbauer, M.J.; Bain, J.R.; Buchwald, P.; Abdulreda, M.H. Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes. Metabolites 2019, 9, 207.

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