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Free fatty acids, insulin resistance, and pregnancy
Abstract
Acute elevation of plasma free fatty acid (FFA) levels causes insulin resistance to rise dose dependently in pregnant and nonpregnant women. Plasma FFA levels are commonly elevated during late pregnancy, partly due to rising blood levels of lipolytic placental hormones, and are a likely cause for much of the increase in insulin resistance occurring at that time in all pregnant women. Plasma FFA levels are similar or higher and the insulin resistance is comparable or more severe in women with gestational diabetes mellitus (GDM) than in nondiabetic pregnant women. In contrast to healthy pregnant women, insulin secretion in women with GDM is defective and, therefore, is unable to rise adequately to compensate for the insulin resistance; the result is hyperglycemia. The mechanism by which elevated plasma FFA levels cause insulin resistance in skeletal muscle includes intramyocellular accumulation of diacylglycerol, which activates protein kinase C (the b II and d isoforms). This results in reduction of tyrosine phosphorylation of the insulin receptor substrate-1 and inhibits activation of phosphoinositol-3 kinase, an enzyme that is essential for normal insulin-stimulated glucose uptake.
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“Saturated fats directly interfere with insulin signaling [41]”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [41]
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“For example, saturated fatty acids increase intracellular concentrations of diacylglycerol within myocytes, activating protein kinase C (PKC) and inhibiting tyrosine kinase, IRS-1 and PI3K [41].”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [41]
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Metadata
- Authors
- Sivan, E., & Boden, G.
- Affiliations
- Temple University Hospital (US)
- ORCID
- Sivan, Eyal
- Venue
- Current Diabetes Reports
- Published
- 2003-07
- Volume
- 3
- Issue
- 4
- Pages
- 319-322
- ISSN
- 1534-4827 (ISSN-L)
- 1539-0829
- OpenAlex
- W2139126524
- Cited by
- 105
- References
- 48
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Diabetes Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01ag015363-05)
- National Institute on Aging (AG15363)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK58895, R01DK058895)
- National Center for Research Resources (M01RR000349, 2 M01 RR00349)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- free fatty acids, insulin resistance, pregnancy, gestational diabetes mellitus, insulin secretion, skeletal muscle, diacylglycerol, protein kinase C, IRS-1, phosphatidylinositol 3-kinase, insulin-stimulated glucose uptake, hyperglycemia
- MeSH terms
- Fatty Acids, Nonesterified, Female, Humans, Insulin, Insulin Resistance, Pregnancy, Diabetes, Gestational, Carbohydrate Metabolism, Lipid Metabolism
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