Cited by 319Lipid metabolism and disordersDiabetes, Cardiovascular Risks, and LipoproteinsLipid metabolism and biosynthesis

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Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM.

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Malmström, R., Packard, C. J., Caslake, M., Bedford, D., Stewart, P., Yki-Järvinen, H., Shepherd, J., Taskinen, M.-R.·1997·Diabetologia

DOI 10.1007/s001250050700

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Abstract

Insulin administration to healthy subjects inhibits the production of very low density lipoprotein (VLDL)1 (Svedbergs flotation (Sf) rate 60-400) without affecting that of VLDL2 (Sf 20-60) sub-class. This study was designed to test whether this hormonal action is impaired in non-insulin-dependent diabetes mellitus (NIDDM). We studied six men with NIDDM (age 53 +/- 3 years, body mass index 27.0 +/- 1.0 kg/m2, plasma triglycerides 1.89 +/- 0.22 mmol/l) during an 8.5 h infusion of saline (control) and then in hyperinsulinaemic (serum insulin approximately 540 pmol/l) conditions during 8.5 h infusions of glucose and insulin to give either hyper- and normoglycaemic conditions. [3-2H]-leucine was used as tracer and kinetic constants derived using a non-steady-state multicompartmental model. Compared to the control study, patients with NIDDM reduced VLDL1 apo B production by only 3 +/- 8% after 8.5 h of hyperinsulinaemia (701 +/- 102 vs 672 +/- 94 mg/day respectively, NS) in hyperglycaemic conditions and by 9 +/- 21% under normoglycaemic conditions (603 +/- 145 mg/day). In contrast, in normal subjects insulin induced a 50 +/- 15% decrement in VLDL1 apo B production (p < 0.05). Direct synthesis of VLDL2 apo B in patients with NIDDM was not markedly affected by insulin. We conclude that a contributory factor to hypertriglyceridaemia in NIDDM is the inability of insulin to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum nonesterfied fatty acids.

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Authors: Malmström, R., Packard, C. J., Caslake, M., Bedford, D., Stewart, P., Yki-Järvinen, H., Shepherd, J., & Taskinen, M.-R.
Affiliations: University of Helsinki (FI)
Glasgow Royal Infirmary (GB)
ORCID: Packard, C. J.
Taskinen, M.-R.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 1997-03-20
Volume: 40
Issue: 4
Pages: 454-462
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s001250050700
OpenAlex: W2167130513
Cited by: 319
References: 39
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 12 · 2015: 12 · 2014: 15 · 2013: 15 · 2012: 12
FWCI: 9.25
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Funders: British Heart Foundation
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: type 2 diabetes, insulin resistance, triglyceride metabolism, VLDL, VLDL1, apolipoprotein B, hepatic lipoprotein secretion, hypertriglyceridemia, hyperinsulinemia, hyperglycemia, free fatty acids
MeSH terms: Apolipoproteins B, Cholesterol, Deuterium, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Humans, Hyperglycemia, Hyperinsulinism, Infusions, Intravenous, Insulin, Leucine, Cholesterol, HDL, Lipoproteins, VLDL, Liver, Male, Middle Aged, Models, Biological, Radioisotope Dilution Technique, Reference Values, Triglycerides, Glucose Clamp Technique

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Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM.

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