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Contributions of gluconeogenesis to glucose production in the fasted state
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Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.
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“In the postabsorptive state, the majority (∼70–75%) of glucose uptake (∼2 mg/kg per min) occurs in insulin-insensitive tissues (brain, erythrocytes, and splanchnic tissues) ( 17 , 18 ), with only ∼25% of glucose uptake occurring in insulin-sensitive tissues.”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [17]
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“Similar approaches focusing on a handful of metabolites have already been used successfully in humans to measure gluconeogenesis and the urea cycle in vivo, and to compare metabolism between lung tumors and surrounding tissue (Fan et al., 2009; Landau et al., 1996; Yudkoff et al., 2010).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Landau et al., 1996
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Metadata
- Authors
- Landau, B. R., Wahren, J., Chandramouli, V, Schumann, W. C., Ekberg, K., & Kalhan, S. C.
- Affiliations
- Case Western Reserve University (US)
- Karolinska University Hospital (SE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1996-07-15
- Volume
- 98
- Issue
- 2
- Pages
- 378-385
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507441
- OpenAlex
- W2040750115
- Cited by
- 487
- References
- 56
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 20 · 2020: 18 · 2019: 14 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 21 · 2014: 17 · 2013: 16 · 2012: 28
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Riksbankens Jubileumsfond
- National Institutes of Health (11089, HD-11089)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-14507)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P-50-HD-11089, P50HD011089)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- gluconeogenesis, glucose production, fasting, deuterium tracer, blood glucose, glycerol, glycogenolysis, pyruvate, glucose-6-phosphate
- MeSH terms
- Adult, Blood Glucose, Chromatography, High Pressure Liquid, Deuterium, Fasting, Female, Gluconeogenesis, Glucose, Glycerol, Humans, Male, Radioisotope Dilution Technique, Time Factors, Xylose
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