Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.
Open accessAbstract
It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.
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Both acute (4-hour) and chronic (4-day) physiological elevation of plasma free fatty acid concentration in insulin-sensitive individuals impairs insulin signalling and causes skeletal muscle insulin resistance.
“Both acute (4 hours) and chronic (4 days) physiologic elevation of plasma FFA concentration in insulin sensitive individuals impairs insulin signaling and causes insulin resistance in skeletal muscle [28, 62–68].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [68]
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- Authors
- Boden, G., & Chen, X.
- Affiliations
- Temple University (US)
- ORCID
- Chen, X
- Venue
- Journal of Clinical Investigation
- Published
- 1995-09-01
- Volume
- 96
- Issue
- 3
- Pages
- 1261-1268
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC185747
- OpenAlex
- W2115830695
- Cited by
- 344
- References
- 39
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 6 · 2015: 13 · 2014: 8 · 2013: 9 · 2012: 14
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01ag007988-10)
- National Institute on Aging (R01-AG07988)
- National Center for Research Resources (M01RR000349, RR-00349)
- 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 › Surgery › Pancreatic function and diabetes
- Keywords
- free fatty acids, insulin resistance, type 2 diabetes, insulin-stimulated glucose uptake, glucose utilization, glucose transport, glycogen synthesis, glycolysis, carbohydrate oxidation, heparin, fat infusion
- MeSH terms
- Aged, Analysis of Variance, Blood Glucose, Diabetes Mellitus, Type 2, Emulsions, Fat Emulsions, Intravenous, Fatty Acids, Nonesterified, Female, Glucagon, Glucose, Heparin, Humans, Infusions, Intravenous, Insulin, Isophane, Male, Middle Aged, Phospholipids, Recombinant Proteins, Safflower Oil, Soybean Oil, Glucose Clamp Technique
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