ArticleMolecular endocrinology (Baltimore, Md.)2012
20-HETE induces hyperglycemia through the cAMP/PKA-PhK-GP pathway.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Gpr75-deficient mice are protected from high-fat diet-induced obesity.Obesity (Silver Spring, Md.) · 2023Article
- 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.Advances in pharmacology (San Diego, Calif.) · 2023Article
- 20-HETE interferes with insulin signaling and contributes to obesity-driven insulin resistance.Prostaglandins & other lipid mediators · 2021Article
- High-fat diet-induced obesity and insulin resistance in CYP4a14American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- 20-HETE: Hypertension and Beyond.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction.American journal of physiology. Heart and circulatory physiology · 2017Article
- Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance.Molecular and cellular biology · 2016Article
- 20-HETE attenuates the response of glucose-stimulated insulin secretion through the AKT/GSK-3β/Glut2 pathway.Endocrine · 2016Article
- CYP4F2 (rs2108622) Gene Polymorphism Association with Age-Related Macular Degeneration.Advances in medicine · 2016Article
- Molecular determinants of acute kidney injury.Journal of injury & violence research · 2015Review
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- Targeting 20-HETE producing enzymes in cancer - rationale, pharmacology, and clinical potential.OncoTargets and therapy · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously generated cytochrome P450 4F2 (CYP4F2) transgenic mice and showed high 20-hydroxyeicosatetraenoic acid (20-HETE) production, which resulted in an elevation of blood pressure. However, it was unclear whether 20-HETE affected glucose metabolism. We measured fasting plasma glucose, insulin, hepatic CYP4F2 expression, and 20-HETE production by hepatic microsomes, and hepatic 20-HETE levels in transgenic mice. We also assessed glycogen phosphorylase (GP) activity and the cAMP/protein kinase A (PKA)-phosphorylase kinase (PhK)-GP pathway, as well as expressions of insulin receptor substrate 1 and glucose transporters in vivo and in vitro. The transgenic mice had overexpressed hepatic CYP4F2, high hepatic 20-HETE and fasting plasma glucose levels but normal insulin level. The GP activity was increased and the cAMP/PKA-PhK-GP pathway was activated in the transgenic mice compared with wild-type mice. Moreover, these alterations were eliminated with the addition of N-hydroxy-N'-(4-butyl-2 methylphenyl) formamidine, which is a selective 20-HETE inhibitor. The results were further validated in Bel7402 cells. In addition, the transgenic mice had functional insulin signaling, and 20-HETE had no effect on insulin signaling in Bel7402 cells, excluding that the observed hyperglycemia in CYP4F2 transgenic mice resulted from insulin dysfunction, because the target tissues were sensitive to insulin. Our study suggested that 20-HETE can induce hyperglycemia, at least in part, through the cAMP/PKA-PhK-GP pathway but not through the insulin-signaling pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.