Disordered lipid metabolism and the pathogenesis of insulin resistance.
Open accessAbstract
Although abnormal glucose metabolism defines type 2 diabetes mellitus (T2DM) and accounts for many of its symptoms and complications, efforts to understand the pathogenesis of T2DM are increasingly focused on disordered lipid metabolism. Here we review recent human studies exploring the mechanistic links between disorders of fatty acid/lipid metabolism and insulin resistance. As “mouse models of insulin resistance” were comprehensively reviewed in Physiological Reviews by Nandi et al. in 2004, we will concentrate on human studies involving the use of isotopes and/or magnetic resonance spectroscopy, occasionally drawing on mouse models which provide additional mechanistic insight.
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Lipid excess has been linked experimentally to induction of insulin resistance and alterations in insulin signal transduction.
“Moreover, lipid excess has been linked experimentally to induction of insulin resistance (96) and alterations in insulin signal transduction (97-99).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [97]
Increased tissue lipid load, as with obesity and/or sustained inactivity, may lead to accumulation of fatty acyl CoA, diacylglycerols, ceramides, products of incomplete oxidation, and ROS, all of which have been linked experimentally to reduced insulin signaling and action.
“Increased tissue lipid load, as with obesity, and/or sustained inactivity, may lead to the accumulation of fatty acyl coenzyme A (CoA), diacylglycerols, ceramides, products of incomplete oxidation, and ROS, all of which have been linked experimentally to reduced insulin signaling and action (96 -102).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [97]
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- Authors
- Savage, D. B., Petersen, K. F., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2007-04
- Volume
- 87
- Issue
- 2
- Pages
- 507-520
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- PMC
- PMC2995548
- OpenAlex
- W2140434971
- Semantic Scholar
- cfe1df09de88f84f92dbe78c17c8dfc35e2dc65b
- Cited by
- 1,107
- References
- 143
- Citations by year
- 2026: 20 · 2025: 48 · 2024: 53 · 2023: 50 · 2022: 40 · 2021: 39 · 2020: 60 · 2019: 43 · 2018: 48 · 2017: 63 · 2016: 37 · 2015: 58 · 2014: 63 · 2013: 92 · 2012: 83
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Institute on Aging (R01-AG-23686, R01AG023686)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049230, R01-DK40936, U24DK59635, R01DK040936, U24DK059635, R01 DK-49230, P01-DK-68829)
- National Center for Research Resources (M01RR000125, M01 RR-00125)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- insulin resistance, type 2 diabetes, lipid metabolism, fatty acid metabolism, glucose metabolism, pathogenesis, isotope tracers, magnetic resonance spectroscopy, human subjects research
- MeSH terms
- Adipose Tissue, Animals, Fatty Acids, Glucose, Humans, Insulin Resistance, Liver, Muscles, Magnetic Resonance Spectroscopy, Obesity, Lipid Metabolism Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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