Document Detail


Metabolomic analysis of pancreatic β-cell insulin release in response to glucose.
MedLine Citation:
PMID:  22847496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Defining the key metabolic pathways that are important for fuel-regulated insulin secretion is critical to providing a complete picture of how nutrients regulate insulin secretion. We have performed a detailed metabolomics study of the clonal β-cell line 832/13 using a gas chromatography-mass spectrometer (GC-MS) to investigate potential coupling factors that link metabolic pathways to insulin secretion. Mid-polar and polar metabolites, extracted from the 832/13 β-cells, were derivatized and then run on a GC/MS to identify and quantify metabolite concentrations. Three hundred fifty-five out of 527 chromatographic peaks could be identified as metabolites by our metabolomic platform. These identified metabolites allowed us to perform a systematic analysis of key pathways involved in glucose-stimulated insulin secretion (GSIS). Of these metabolites, 41 were consistently identified as biomarker for GSIS by orthogonal partial least-squares (OPLS). Most of the identified metabolites are from common metabolic pathways including glycolytic, sorbitol-aldose reductase pathway, pentose phosphate pathway, and the TCA cycle suggesting these pathways play an important role in GSIS. Lipids and related products were also shown to contribute to the clustering of high glucose sample groups. Amino acids lysine, tyrosine, alanine and serine were upregulated by glucose whereas aspartic acid was downregulated by glucose suggesting these amino acids might play a key role in GSIS. In summary, a coordinated signaling cascade elicited by glucose metabolism in pancreatic β-cells is revealed by our metabolomics platform providing a new conceptual framework for future research and/or drug discovery.
Authors:
Mei Huang; Jamie W Joseph
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Islets     Volume:  4     ISSN:  1938-2022     ISO Abbreviation:  Islets     Publication Date:    2012 May-Jun
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-03-08     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  101495366     Medline TA:  Islets     Country:  United States    
Other Details:
Languages:  eng     Pagination:  210-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Diabetes Mellitus, Type 1 / metabolism*
Gas Chromatography-Mass Spectrometry / methods
Glucose / administration & dosage*,  metabolism
Insulin / metabolism*,  secretion
Insulin-Secreting Cells / metabolism*
Metabolomics / methods
Principal Component Analysis
Rats
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Insulin; IY9XDZ35W2/Glucose
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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