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Cited by 786Muscle metabolism and nutritionCardiovascular and exercise physiologyExercise and Physiological Responses

Substrate Turnover during Prolonged Exercise in Man

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Ahlborg, Gunvor, Felig, Philip, Hagenfeldt, Lars, Hendler, Rosa, Wahren, John·1974·Journal of Clinical Investigation
DOI 10.1172/jci107645PMC PMC333093
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Abstract

Arterial concentrations and substrate exchange across the leg and splanchnic vascular beds were determined for glucose, lactate, pyruvate, glycerol, individual acidic and neutral amino acids, and free fatty acids (FFA) in six subjects at rest and during 4 h of exercise at approximately 30% of maximal oxygen uptake. FFA turnover and regional exchange were evaluated using (14)C-labeled oleic acid. The arterial glucose concentration was constant for the first 40 min of exercise, but fell progressively thereafter to levels 30% below basal. The arterial insulin level decreased continuously, while the arterial glucagon concentration had risen fivefold after 4 h of exercise. Uptake of glucose and FFA by the legs was markedly augmented during exercise, the increase in FFA uptake being a consequence of augmented arterial levels rather than increased fractional extraction. As exercise was continued beyond 40 min, the relative contribution of FFA to total oxygen metabolism rose progressively to 62%. In contrast, the contribution from glucose fell from 40% to 30% between 90 and 240 min. Leg output of alanine increased as exercise progressed. Splanchnic glucose production, which rose 100% above basal levels and remained so throughout exercise, exceeded glucose uptake by the legs for the first 40 min but thereafter failed to keep pace with peripheral glucose utilization. Total estimated splanchnic glucose output was 75 g in 4 h, sufficient to deplete approximately 75% of liver glycogen stores. Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol, alanine) had increased 2- to 10-fold after 4 h of exercise, and was sufficient to account for 45% of glucose release at 4 h as compared to 20-25% at rest and at 40 min of exercise. In the case of alanine and lactate, the increase in precursor uptake was a consequence of a rise in splanchnic fractional extraction. It is concluded that during prolonged exercise at a low work intensity (a) blood glucose levels fall because hepatic glucose output fails to keep up with augmented glucose utilization by the exercising legs; (b) a large portion of hepatic glycogen stores is mobilized and an increasing fraction of the splanchnic glucose output is derived from gluconeogenesis; (c) blood-borne substrates in the form of glucose and FFA account for a major part of leg muscle metabolism, the relative contribution from FFA increasing progressively; and (d) augmented secretion of glucagon may play an important role in the metabolic adaptation to prolonged exercise by its stimulatory influence on hepatic glycogenolysis and gluconeogenesis.

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  • During the glucose alanine cycle, alanine is shuttled to the liver via the bloodstream and converted into pyruvate through a transamination reaction catalysed by the action of glutamate-pyruvate aminotransferase.

    “During this process, alanine is shuttled to the liver via the bloodstream and converted into pyruvate through a transamination reaction catalysed by the action of glutamate-pyruvate aminotransferase.”

    From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [98]

    The Results and discussion (page unavailable) report alanine release by the exercising leg and uptake by splanchnic tissues, consistent with its transport through the blood toward the liver. Our copy does not describe alanine’s conversion to pyruvate by transamination or name glutamate-pyruvate aminotransferase. (LLM, conf=0.86)

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  • At low (approximately 30% VO2max) exercise intensities, splanchnic glucose production was sufficient to deplete 75% of the liver glycogen stores.

    “The remarkable contribution of these carbohydrate sources with prolonged duration is seen even at low (≈30% VO2max) exercise intensities, whereby splanchnic glucose production was sufficient to deplete 75% of the liver glycogen stores [98].”

    From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [98]

  • Lactate is an important precursor for hepatic gluconeogenesis and the production of glucose during exercise, which may subsequently undergo oxidation.

    “However, as a glycolytic end product in muscle, lactate is an important precursor for hepatic gluconeogenesis and the production of glucose during exercise, which may subsequently undergo oxidation [98,124].”

    From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [98]

  • Pyruvate can then act as metabolic substrate via a gluconeogenic pathway, where the newly formed glucose can boost exercising muscles for their energy demands.

    “Pyruvate can then act as metabolic substrate via a gluconeogenic pathway, where the newly formed glucose can boost exercising muscles for their energy demands.”

    From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [98]

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Authors
Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R., & Wahren, J.
Affiliations
Karolinska Institutet (SE)
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1974-04-01
Volume
53
Issue
4
Pages
1080-1090
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci107645
PMC
PMC333093
OpenAlex
W2135191741
Cited by
786
References
42
Citations by year
2026: 9 · 2025: 8 · 2024: 13 · 2023: 16 · 2022: 18 · 2021: 17 · 2020: 13 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 14 · 2014: 20 · 2013: 23 · 2012: 13
FWCI
8.28
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
prolonged exercise, substrate turnover, free fatty acid uptake, glucose utilization, gluconeogenesis, insulin, glucagon, alanine, lactate, pyruvate, glycerol, amino acids, fatty acid oxidation, oxygen metabolism, fractional extraction, leg blood flow, splanchnic circulation
MeSH terms
Abdomen, Adult, Amino Acids, Arteries, Blood Flow Velocity, Blood Glucose, Carbon Radioisotopes, Physical Exertion, Fatty Acids, Nonesterified, Glucagon, Glycerol, Heart Rate, Humans, Insulin, Lactates, Leg, Male, Oleic Acids, Oxygen Consumption, Pyruvates, Time Factors

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