CoChat
Sign Up
Cited by 487Diabetes, Cardiovascular Risks, and LipoproteinsMuscle metabolism and nutritionAdipose Tissue and Metabolism

Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus.

Open access
Kelley, D E, Simoneau, J A·1994·Journal of Clinical Investigation
DOI 10.1172/jci117600PMC PMC330064
Open this paper in CoChat — free accountOpen PDF

Abstract

This study was undertaken to assess utilization of FFA by skeletal muscle in patients with non-insulin-dependent diabetes mellitus (NIDDM). 11 NIDDM and 9 nondiabetic subjects were studied using leg balance methods to measure the fractional extraction of [3H]oleate. Limb indirect calorimetry was used to estimate RQ. Percutaneous muscle biopsy samples of vastus lateralis were analyzed for muscle fiber type distribution, capillary density, and metabolic potential as reflected by measurements of the activity of seven muscle enzyme markers of glycolytic and aerobic-oxidative pathways. During postabsorptive conditions, fractional extraction of oleate across the leg was lower in NIDDM subjects (0.31 +/- 0.08 vs. 0.43 +/- 0.10, P < 0.01), and there was reduced oleate uptake across the leg (66 +/- 8 vs. 82 +/- 13 nmol/min, P < 0.01). Postabsorptive leg RQ was increased in NIDDM (0.85 +/- 0.03 vs. 0.77 +/- 0.02, P < 0.01), and rates of lipid oxidation by skeletal muscle were lower while glucose oxidation was increased (P < 0.05). In subjects with NIDDM, proportions of type I, IIa, and IIb fibers were 37 +/- 2, 37 +/- 6, and 26 +/- 5%, respectively, which did not differ from nondiabetics; and capillary density, glycolytic, and aerobic-oxidative potentials were similar. During 6 h after ingestion of a mixed meal, arterial FFA remained greater in NIDDM subjects. Therefore, despite persistent reduced fractional extraction of oleate across the leg in NIDDM (0.34 +/- 0.04 vs. 0.38 +/- 0.03, P < 0.05), rates of oleate uptake across the leg were greater in NIDDM (54 +/- 7 vs. 45 +/- 8 nmol/min, P < 0.01). In summary, during postabsorptive conditions there is reduced utilization of FFA by muscle, while during postprandial conditions there is impaired suppression of FFA uptake across the leg in NIDDM. During both fasting and postprandial conditions, NIDDM subjects have reduced rates of lipid oxidation by muscle.

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/jci117600

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

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?

  • Insulin resistance associated with obesity and type 2 diabetes is characterized by reduced oxidative capacities in skeletal muscle.

    “Interestingly, insulin resistance associated with obesity and type 2 diabetes is characterized by reduced oxidative capacities in skeletal muscle (1,9,13).”

    From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [1]

    The Discussion says that enzyme markers of aerobic-oxidative capacity were equivalent in subjects with type 2 diabetes and nondiabetic subjects; none of the seven enzymes assayed differed significantly. The paper reports reduced skeletal-muscle lipid oxidation in diabetes, but distinguishes that finding from reduced oxidative capacity. It does not establish the claim for obesity. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Beta-oxidation accounts for 80% of the total energy-related oxidation in skeletal muscle at rest after an overnight fast, and this percentage increases further in response to prolonged fasting.

    “Beta-oxidation accounts for 80% of the total energy-related oxidation in skeletal muscle at rest after an overnight fast, and this percentage increases further in response to prolonged fasting (Kelley and Simoneau, 1994).”

    From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Kelley and Simoneau, 1994

    The Methods describe an overnight fast, and the results report that lipid oxidation accounted for 77±6% of basal leg oxygen consumption in nondiabetic subjects, supporting the approximately 80% figure. The paper does not report a further increase with prolonged fasting; it compares the postabsorptive state with the period after a meal. The cited passages do not provide page numbers. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • During insulin stimulation, obese individuals and patients with T2DM cannot increase RER to the same extent as lean individuals.

    “during insulin stimulation, obese individuals and patients with T2DM are not able to increase the RER value to the same extent as lean individuals”

    From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Kelley and Simoneau, 1994

    The Results report a smaller numerical rise in leg respiratory quotient (RQ) after a mixed meal in the NIDDM group (0.85 to 0.87) than in nondiabetic controls (0.77 to 0.81). But this was a meal study, not a direct test of RQ during insulin stimulation, and the Methods say the groups did not differ in degree of obesity; the paper does not establish the claimed obese-versus-lean comparison. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Human type 2 diabetes is associated with reduced capacity to oxidize glucose in the presence of insulin and to oxidize fatty acid in various conditions.

    “Human type 2 diabetes is associated with reduced capacity to oxidize glucose in the presence of insulin and, more importantly, to oxidize fatty acid in various conditions (1,2).”

    From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [1]

    The Introduction and Results report reduced skeletal-muscle lipid oxidation in people with NIDDM during both fasting and postprandial conditions. The paper does not establish reduced glucose oxidation in the presence of insulin; its Results instead report higher leg glucose oxidation in the NIDDM group under the conditions studied. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In those studies, people with T2D showed larger rises in circulating NEFA but lower lipid oxidation than controls (19).

    “In that approach, subjects with T2D had higher increases in circulating NEFA levels, but lower lipid oxidation, than control subjects (19).”

    From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [19]

Self-check

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

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

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kelley, D. E., & Simoneau, J. A.
Affiliations
  • Veterans Health Administration (US)
  • Université Laval (CA)
ORCID
Kelley, D E
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1994-12-01
Volume
94
Issue
6
Pages
2349-2356
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci117600
PMC
PMC330064
OpenAlex
W2112522013
Cited by
487
References
45
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 19 · 2021: 18 · 2020: 12 · 2019: 8 · 2018: 11 · 2017: 22 · 2016: 17 · 2015: 24 · 2014: 17 · 2013: 21 · 2012: 21
FWCI
4.10
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • U.S. Department of Veterans Affairs
  • National Institutes of Health
  • Fonds de Recherche du Québec - Santé
  • National Center for Research Resources (M01RR000056, 5 MO1 RR 00056)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
type 2 diabetes, skeletal muscle, oleate uptake, fractional extraction, lipid oxidation, glucose oxidation, respiratory quotient, muscle fiber type distribution, capillary density, muscle enzyme activity, vastus lateralis, indirect calorimetry, muscle biopsy
MeSH terms
Blood Glucose, Calorimetry, Indirect, Diabetes Mellitus, Type 2, Fasting, Fatty Acids, Nonesterified, Female, Humans, Hyperglycemia, Insulin, Leg, Male, Middle Aged, Models, Biological, Oleic Acids, Oxidation-Reduction, Triglycerides, Muscle, Skeletal, Muscle Fibers, Skeletal, Oleic 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