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Cited by 181Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerDiabetes Treatment and Management

The DOI matches its Crossref record; 54 of the 55 references it cites were found in a registry or an index.

Effect of a Sustained Reduction in Plasma Free Fatty Acid Concentration on Intramuscular Long-Chain Fatty Acyl-CoAs and Insulin Action in Type 2 Diabetic Patients

Bajaj, Mandeep, Suraamornkul, Swangjit, Romanelli, Anthony, Cline, Gary W., Mandarino, Lawrence J., Shulman, Gerald I., DeFronzo, Ralph A.·2005·Diabetes
DOI 10.2337/diabetes.54.11.3148
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Abstract

To investigate the effect of a sustained (7-day) decrease in plasma free fatty acid (FFA) concentrations on insulin action and intramyocellular long-chain fatty acyl-CoAs (LCFA-CoAs), we studied the effect of acipimox, a potent inhibitor of lipolysis, in seven type 2 diabetic patients (age 53 ± 3 years, BMI 30.2 ± 2.0 kg/m2, fasting plasma glucose 8.5 ± 0.8 mmol/l, HbA1c 7.5 ± 0.4%). Subjects received an oral glucose tolerance test (OGTT) and 120-min euglycemic insulin (80 mU/m2 per min) clamp with 3-[3H]glucose/vastus lateralis muscle biopsies to quantitate rates of insulin-mediated whole-body glucose disposal (Rd) and intramyocellular LCFA-CoAs before and after acipimox (250 mg every 6 h for 7 days). Acipimox significantly reduced fasting plasma FFAs (from 563 ± 74 to 230 ± 33 μmol/l; P < 0.01) and mean plasma FFAs during the OGTT (from 409 ± 44 to 184 ± 22 μmol/l; P < 0.01). After acipimox, decreases were seen in fasting plasma insulin (from 78 ± 18 to 42 ± 6 pmol/l; P < 0.05), fasting plasma glucose (from 8.5 ± 0.8 to 7.0 ± 0.5 mmol/l; P < 0.02), and mean plasma glucose during the OGTT (from 14.5 ± 0.8 to 13.0 ± 0.8 mmol/l; P < 0.05). After acipimox, insulin-stimulated Rd increased from 3.3 ± 0.4 to 4.4 ± 0.4 mg · kg−1 · min−1 (P < 0.03), whereas suppression of endogenous glucose production (EGP) was similar and virtually complete during both insulin clamp studies (0.16 ± 0.10 vs. 0.14 ± 0.10 mg · kg−1 · min−1; P > 0.05). Basal EGP did not change after acipimox (1.9 ± 0.2 vs. 1.9 ± 0.2 mg · kg−1 · min−1). Total muscle LCFA-CoA content decreased after acipimox treatment (from 7.26 ± 0.58 to 5.64 ± 0.79 nmol/g; P < 0.05). Decreases were also seen in muscle palmityl CoA (16:0; from 1.06 ± 0.10 to 0.75 ± 0.11 nmol/g; P < 0.05), palmitoleate CoA (16:1; from 0.48 ± 0.05 to 0.33 ± 0.05 nmol/g; P = 0.07), oleate CoA (18:1; from 2.60 ± 0.11 to 1.95 ± 0.31 nmol/g; P < 0.05), linoleate CoA (18:2; from 1.81 ± 0.26 to 1.38 ± 0.18 nmol/g; P = 0.13), and linolenate CoA (18:3; from 0.27 ± 0.03 to 0.19 ± 0.02 nmol/g; P < 0.03) levels after acipimox treatment. Muscle stearate CoA (18:0) did not decrease after acipimox treatment. The increase in Rd correlated strongly with the decrease in muscle palmityl CoA (r = 0.75, P < 0.05), oleate CoA (r = 0.76, P < 0.05), and total muscle LCFA-CoA (r = 0.74, P < 0.05) levels. Plasma adiponectin did not change significantly after acipimox treatment (7.9 ± 1.8 vs. 7.5 ± 1.5 μg/ml). These data demonstrate that the reduction in intramuscular LCFA-CoA content is closely associated with enhanced insulin sensitivity in muscle after a chronic reduction in plasma FFA concentrations in type 2 diabetic patients despite the lack of an effect on plasma adiponectin concentration.

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Metadata

Authors
Bajaj, M., Suraamornkul, S., Romanelli, A., Cline, G. W., Mandarino, L. J., Shulman, G. I., & DeFronzo, R. A.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • Howard Hughes Medical Institute (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2005-11-01
Volume
54
Issue
11
Pages
3148-3153
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.54.11.3148
OpenAlex
W2160930691
Cited by
181
References
55
Citations by year
2026: 2 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 6 · 2013: 9 · 2012: 11
FWCI
8.49
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 45735, DK 24092, DK-068229, P30DK045735, P01DK068229)
  • National Center for Research Resources (M01RR01346, M01RR001346)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 2 diabetes, plasma free fatty acids, acipimox, lipolysis inhibition, long-chain fatty acyl-CoA, intramyocellular lipid, insulin action, insulin sensitivity, glucose disposal, insulin-stimulated glucose uptake, endogenous glucose production, insulin resistance, hyperinsulinemic-euglycemic clamp, oral glucose tolerance test, fatty acid oxidation
MeSH terms
Acyl Coenzyme A, Hypolipidemic Agents, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Glucose Tolerance Test, Humans, Hyperlipidemias, Insulin, Male, Middle Aged, Pyrazines, Muscle, Skeletal, Adiponectin

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