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Cited by 1,050Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsLipid metabolism and disorders

Effect of fatty acids on glucose production and utilization in man.

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Ferrannini, E, Barrett, E J, Bevilacqua, S, DeFronzo, R A·1983·Journal of Clinical Investigation
DOI 10.1172/jci111133PMC PMC370462
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Abstract

Since the initial proposal of the glucose fatty acid cycle, considerable controversy has arisen concerning its physiologic significance in vivo. In the present study, we examined the effect of acute, physiologic elevations of FFA concentrations on glucose production and uptake in normal subjects under three controlled experimental conditions. In group A, plasma insulin levels were raised and maintained at approximately 100 microU/ml above base line by an insulin infusion, while holding plasma glucose at the fasting level by a variable glucose infusion. In group B, plasma glucose concentration was raised by 125 mg/100 ml and plasma insulin was clamped at approximately 50 microU/ml by a combined infusion of somatostatin and insulin. In group C, plasma glucose was raised by 200 mg/100 ml above the fasting level, while insulin secretion was inhibited with somatostatin and peripheral glucagon levels were replaced with a glucagon infusion (1 ng/min X kg). Each protocol was repeated in the same subject in combination with a lipid-heparin infusion designed to raise plasma FFA levels by 1.5-2.0 mumol/ml. With euglycemic hyperinsulinemia (study A), lipid infusion caused a significant inhibition of total glucose uptake (6.3 +/- 1.3 vs. 7.4 +/- 0.6 mg/min X kg, P less than 0.02). Endogenous glucose production (estimated by the [3-3H]glucose technique) was completely suppressed both with and without lipid infusion. With hyperglycemic hyperinsulinemia (study B), lipid infusion also induced a marked impairment in glucose utilization (6.2 +/- 1.1 vs. 9.8 +/- 1.9 mg/min X kg, P less than 0.05); endogenous glucose production was again completely inhibited despite the increase in FFA concentrations. Under both conditions (A and B), the percentage inhibition of glucose uptake by FFA was positively correlated with the total rate of glucose uptake (r = 0.69, P less than 0.01). In contrast, when hyperglycemia was associated with relative insulinopenia and hyperglucagonemia (study C), thus simulating a diabetic state, lipid infusion had no effect on glucose uptake (2.9 +/- 0.2 vs. 2.6 +/- 0.2 mg/min X kg) but markedly stimulated endogenous glucose production (1.4 +/- 0.5 vs. 0.5 +/- 0.4 mg/min X kg, P less than 0.005). Under the same conditions as study C, a glycerol infusion producing plasma glycerol levels similar to those achieved with lipid-heparin, enhanced endogenous glucose production (1.5 +/- 0.5 vs. 0.7 +/- 0.6 mg/min X kg, P less than 0.05). We conclude that, in the well-insulinized state raised FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. When insulin is deficient, on the other hand, elevated rates of lipolysis may contribute to hyperglycemia not by competition for fuel utilization, but through an enhancement of endogenous glucose output.

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  • Patients with higher BMI have more fat tissue, which has a relatively low glucose uptake during the fasting state.

    “Moreover, patients with higher BMI have more fat tissue, which has a relatively low glucose uptake during fasting state [91,92].”

    From Effect of blood glucose level on standardized uptake value (SUV) in 18F-FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements (2019) · cites this paper as [92]

    The Subjects section describes healthy volunteers within 20% of desirable body weight, not patients grouped by BMI. The Discussion addresses how free fatty acids affect glucose uptake chiefly in muscle; our copy does not address whether higher-BMI patients have more fat tissue or whether fat tissue has relatively low glucose uptake during fasting. Searches for adipose-tissue uptake and BMI or adiposity found no passage establishing those points. (LLM, conf=0.74)

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Research works printed but not linked: 2

  1. Pilo, A., E. Ferrannini, 0. Bjorkman, J. Wahren, C. A. Reichard, P. Felig, and R. A. DeFronzo. 1981. Analysis of glucose production and disappearance rates following an oral glucose load in normal subjects: a double tracer approach. In Carbohydrate Metabolism: Quantitative Physiology and Mathematical Modelling. C. Cobelli and R. N. Bergman, editors. John Wiley & Sons, Ltd., Lon- don. 221-228.
  2. Bergmeyer, H. V. 1974. Methods of Enzymatic Analysis. Academic Press, Inc., New York. 3:1836-1839.

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Authors
Ferrannini, E., Barrett, E. J., Bevilacqua, S., & DeFronzo, R. A.
Affiliations
  • Yale University (US)
  • University of Pisa (IT)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1983-11-01
Volume
72
Issue
5
Pages
1737-1747
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci111133
PMC
PMC370462
OpenAlex
W2130200187
Cited by
1,050
References
60
Citations by year
2026: 5 · 2025: 5 · 2024: 14 · 2023: 7 · 2022: 16 · 2021: 22 · 2020: 18 · 2019: 19 · 2018: 18 · 2017: 16 · 2016: 20 · 2015: 21 · 2014: 13 · 2013: 13 · 2012: 24
FWCI
13.34
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders
National Institutes of Health (5r01am024092-06, 2r01am020495-09a1)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
free fatty acids, glucose production, glucose uptake, glucose-fatty acid cycle, insulin, hyperinsulinemia, hyperglycemia, insulin deficiency, glucagon, lipid infusion, hyperinsulinemic-euglycemic clamp, somatostatin, diabetes mellitus, hepatic glucose metabolism, peripheral glucose utilization, hepatic glucose utilization, hepatic lipogenesis, hepatic gluconeogenesis
MeSH terms
Adolescent, Adult, Blood Glucose, Fat Emulsions, Intravenous, Fatty Acids, Nonesterified, Female, Glucose, Glycerol, Heparin, Humans, Hydroxybutyrates, Insulin, Male, Somatostatin, Triglycerides, 3-Hydroxybutyric Acid

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