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

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

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

Open access
Ferrannini, E, Barrett, E J, Bevilacqua, S, DeFronzo, R A·1983·Journal of Clinical Investigation
DOI 10.1172/jci111133PMC PMC370462
Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1172/jci111133

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 60 references

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.

Cited by

Sorted by citations

Items 201–300 of 1,001

Related

See all

Metadata

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 › Endocrinology, Diabetes and Metabolism › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review