Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans
Abstract
Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1-14C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH14CO3 prime) to achieve steady-state conditions of 14CO2 yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH14CO3 infusion, calculated rates of 14CO2 appearance agreed closely with NaH14CO3 infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60-120 min. In study 4, plasma insulin concentration was raised to 14 +/- 2, 23 +/- 2, 38 +/- 2, 72 +/- 5, and 215 +/- 10 microU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose-dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to…
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Lipolysis is more sensitive to small changes in insulin concentration than EGP, and plasma NEFA levels are closely correlated with changes in lipolysis.
“As lipolysis is more sensitive to small changes in insulin concentration than EGP [35, 36], and plasma NEFA levels are closely correlated with changes in lipolysis”
From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [35]
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Result7 Insulin action and substrate competition
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“In fact, true IC TG/FA cycling rates may be even lower because the calculations assumed that all ing numerous reports by others (25,30-33).”
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“Insulin resistance and hyperinsulinemia are early precursors to type 2 diabetes and are thought to precede diabetes associated hyperglycaemia.(19) Examining weight along the spectrum of hyperinsulinemia and insulin resistance allows analysis of weight change along a timeline to where insulin begins to rise.”
BackgroundInfluentialAnti Hyperlipidemic Activities Of Annona Muricata (Linn)
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“In our study after mixed load, plasma FFA remained signi®cantly higher than after glucose alone (Figure 3c), despite the rise of circulating insulin to concentrations that have been demonstrated to inhibit lipolysis (Chen et al, 1987; Bonadonna et al, 1990).”
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“The low insulin environment appears to be a critical contributor to these observations as low blood insulin concentrations (Bonadonna et al., 1990; Campbell et al., 1992; Horowitz et al., 1997; Weltan et al., 1998) favor increased adipose tissue lipolysis resulting in increased FFA availability, thereby providing incr…”
BackgroundEffect of Fat Intake on Energy Balance
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“Resting-state plasma FFA concentration is directly linked to the peak fat oxidation rate (34, 35).”
Oscillations of Fatty Acid and Glycerol Release From Human Subcutaneous Adipose Tissue In Vivo
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“In addition, the half-life of plasma NEFA in humans, for instance, is 3 min (17,18), so a peak might convert to a nadir within a few minutes.”
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“Suppression of endogenous glucose production (EGP) after 4 h of hyperinsulinemia was 68 ± 14% (from 13.3 ± 2.2 to 4.3 ± 2.1 µmol kg 1 min 1) during the Prestudy, 100 ± 12% (from 10.9 ± 0.6 to 0.0 ± 1.2 µmol kg 1 min 1) during the thalidomide study, and 93 ± 12% (from 14.5 ± 2.0 to 1.0 ± 18 µmol kg 1 min 1) during the…”
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“Indeed, glycemia may comprise a gross biomarker of adaptation, relatively less sensitive to insulin action than lipolysis (32).”
BackgroundEffect of glycemic index on whole-body substrate oxidation in obese women
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- Authors
- Bonadonna, R. C., Groop, L. C., Zych, K., Shank, M., & DeFronzo, R. A.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 1990-11-01
- Volume
- 259
- Issue
- 5
- Pages
- E736-E750
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W1872660062
- Cited by
- 149
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 3 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AM 24 092, 5r01am024092-06)
- National Center for Research Resources (RR 125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin, plasma free fatty acids, fatty acid turnover, fatty acid oxidation, lipid oxidation, hepatic glucose production, glucose disposal, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Body Height, Body Weight, Calorimetry, Child, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Female, Glucose, Humans, Insulin, Kinetics, Liver, Male, Oxidation-Reduction, Reference Values, Time Factors
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