Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity
Abstract Glucose ingestion after an overnight fast triggers an insulin‐dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry‐based strategy to simultaneously mea...
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| Format: | Article |
| Language: | English |
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Springer Nature
2008-08-01
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| Series: | Molecular Systems Biology |
| Online Access: | https://doi.org/10.1038/msb.2008.50 |
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| _version_ | 1849225748378812416 |
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| author | Oded Shaham Ru Wei Thomas J Wang Catherine Ricciardi Gregory D Lewis Ramachandran S Vasan Steven A Carr Ravi Thadhani Robert E Gerszten Vamsi K Mootha |
| author_facet | Oded Shaham Ru Wei Thomas J Wang Catherine Ricciardi Gregory D Lewis Ramachandran S Vasan Steven A Carr Ravi Thadhani Robert E Gerszten Vamsi K Mootha |
| author_sort | Oded Shaham |
| collection | DOAJ |
| description | Abstract Glucose ingestion after an overnight fast triggers an insulin‐dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry‐based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre‐diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's ‘insulin response profile’, which could have value in predicting diabetes, its complications, and in guiding therapy. |
| format | Article |
| id | doaj-art-22e17afba041436bbd5aa00b54151fa7 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2008-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-22e17afba041436bbd5aa00b54151fa72025-08-24T12:01:39ZengSpringer NatureMolecular Systems Biology1744-42922008-08-01411910.1038/msb.2008.50Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivityOded Shaham0Ru Wei1Thomas J Wang2Catherine Ricciardi3Gregory D Lewis4Ramachandran S Vasan5Steven A Carr6Ravi Thadhani7Robert E Gerszten8Vamsi K Mootha9Broad Institute of MIT and HarvardBroad Institute of MIT and HarvardFramingham Heart Study, National Heart Lung and Blood Institute and Boston UniversityGeneral Clinical Research Center, Massachusetts Institute of TechnologyBroad Institute of MIT and HarvardFramingham Heart Study, National Heart Lung and Blood Institute and Boston UniversityBroad Institute of MIT and HarvardGeneral Clinical Research Center, Massachusetts Institute of TechnologyBroad Institute of MIT and HarvardBroad Institute of MIT and HarvardAbstract Glucose ingestion after an overnight fast triggers an insulin‐dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry‐based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre‐diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's ‘insulin response profile’, which could have value in predicting diabetes, its complications, and in guiding therapy.https://doi.org/10.1038/msb.2008.50 |
| spellingShingle | Oded Shaham Ru Wei Thomas J Wang Catherine Ricciardi Gregory D Lewis Ramachandran S Vasan Steven A Carr Ravi Thadhani Robert E Gerszten Vamsi K Mootha Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity Molecular Systems Biology |
| title | Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| title_full | Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| title_fullStr | Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| title_full_unstemmed | Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| title_short | Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| title_sort | metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity |
| url | https://doi.org/10.1038/msb.2008.50 |
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