Feasibility of localized metabolomics in the study of pancreatic islets and diabetes

Oscar Alcazar, Luis F. Hernandez, Ashley Tschiggfrie, Michael J. Muehlbauer, James R. Bain, Peter Buchwald, Midhat H. Abdulreda

Research output: Contribution to journalArticle

Abstract

(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.

Original languageEnglish (US)
Article number207
JournalMetabolites
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

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Metabolomics
Aqueous Humor
Medical problems
Metabolites
Islets of Langerhans
Biomarkers
Transplants
Plasmas
Hyperglycemia
Insulin
Inbred NOD Mouse
Allografts
Animals
Health
Immunity

Keywords

  • Anterior chamber of the eye
  • Autoimmune diabetes
  • GC-MS
  • Gender differences
  • Islet microenvironment
  • Local metabolomics
  • Non-obese diabetic (NOD) mice
  • Non-targeted metabolomics
  • Pancreatic islet
  • T1D biomarkers

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

Cite this

Feasibility of localized metabolomics in the study of pancreatic islets and diabetes. / Alcazar, Oscar; Hernandez, Luis F.; Tschiggfrie, Ashley; Muehlbauer, Michael J.; Bain, James R.; Buchwald, Peter; Abdulreda, Midhat H.

In: Metabolites, Vol. 9, No. 10, 207, 10.2019.

Research output: Contribution to journalArticle

Alcazar, Oscar ; Hernandez, Luis F. ; Tschiggfrie, Ashley ; Muehlbauer, Michael J. ; Bain, James R. ; Buchwald, Peter ; Abdulreda, Midhat H. / Feasibility of localized metabolomics in the study of pancreatic islets and diabetes. In: Metabolites. 2019 ; Vol. 9, No. 10.
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abstract = "(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.",
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AU - Hernandez, Luis F.

AU - Tschiggfrie, Ashley

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AU - Bain, James R.

AU - Buchwald, Peter

AU - Abdulreda, Midhat H.

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N2 - (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.

AB - (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.

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KW - T1D biomarkers

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