ArticleThe Journal of biological chemistry2015
Inhibited insulin signaling in mouse hepatocytes is associated with increased phosphatidic acid but not diacylglycerol.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Phospholipase D: emerging therapeutic targets in signaling, metabolism, and immune-oncology.Cell communication and signaling : CCS · 2025Review
- Untargeted Lipidomic Profiling of Amniotic Fluid Reveals Dysregulated Lipid Metabolism in Healthy Normal-Weight Mothers with Fetal Macrosomia.Nutrients · 2024Article
- Lipidomic signatures in Colombian adults with metabolic syndrome.Journal of diabetes and metabolic disorders · 2024Article
- GPAT1 Activity and Abundant Palmitic Acid Impair Insulin Suppression of Hepatic Glucose Production in Primary Mouse Hepatocytes.The Journal of nutrition · 2024Article
- Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus-The Chicken or the Egg Dilemma.Biomedicines · 2023Review
- New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein.International journal of molecular sciences · 2020Review
- Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1-induced steatosis.The Journal of biological chemistry · 2019Article
- An in vivo screen for neuronal genes involved in obesity identifies Diacylglycerol kinase as a regulator of insulin secretion.Molecular metabolism · 2019Article
- Metabolites as regulators of insulin sensitivity and metabolism.Nature reviews. Molecular cell biology · 2018Review
- Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration.Molecular neurobiology · 2018Article
- Insulin action and resistance in obesity and type 2 diabetes.Nature medicine · 2017Review
- Phospholipase D1 deficiency in mice causes nonalcoholic fatty liver disease via an autophagy defect.Scientific reports · 2016Article
- At the interface of antioxidant signalling and cellular function: Key polyphenol effects.Molecular nutrition & food research · 2016Review
- Disparate metabolic response to fructose feeding between different mouse strains.Scientific reports · 2015Article
- Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.The Journal of clinical investigation · 2015Article
- mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues: effects of obesity and insulin resistance.Physiological reports · 2015Article
- Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D.International journal of endocrinology · 2015Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Although an elevated triacylglycerol content in non-adipose tissues is often associated with insulin resistance, the mechanistic relationship remains unclear. The data support roles for intermediates in the glycerol-3-phosphate pathway of triacylglycerol synthesis: diacylglycerol (DAG), which may cause insulin resistance in liver by activating PKCϵ, and phosphatidic acid (PA), which inhibits insulin action in hepatocytes by disrupting the assembly of mTOR and rictor. To determine whether increases in DAG and PA impair insulin signaling when produced by pathways other than that of de novo synthesis, we examined primary mouse hepatocytes after enzymatically manipulating the cellular content of DAG or PA. Overexpressing phospholipase D1 or phospholipase D2 inhibited insulin signaling and was accompanied by an elevated cellular content of total PA, without a change in total DAG. Overexpression of diacylglycerol kinase-θ inhibited insulin signaling and was accompanied by an elevated cellular content of total PA and a decreased cellular content of total DAG. Overexpressing glycerol-3-phosphate acyltransferase-1 or -4 inhibited insulin signaling and increased the cellular content of both PA and DAG. Insulin signaling impairment caused by overexpression of phospholipase D1/D2 or diacylglycerol kinase-θ was always accompanied by disassociation of mTOR/rictor and reduction of mTORC2 kinase activity. However, although the protein ratio of membrane to cytosolic PKCϵ increased, PKC activity itself was unaltered. These data suggest that PA, but not DAG, is associated with impaired insulin action in mouse hepatocytes.
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