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Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM.
Open accessAbstract
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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“Hepatic insulin resistance may contribute to a high production rate of VLDL because insulin reduces apoB synthesis and VLDL secretion in the liver (66, 67).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [66]
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Metadata
- 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)
- Venue
- Diabetologia
- Published
- 1997-03-20
- Volume
- 40
- Issue
- 4
- Pages
- 454-462
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- 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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