Evidence map›Paper›PMID 22918876›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2012

20-HETE induces hyperglycemia through the cAMP/PKA-PhK-GP pathway.

Guangrui Lai, Jingjing Wu, Xiaoliang Liu, Yanyan Zhao

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. 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 · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. High-fat diet-induced obesity and insulin resistance in CYP4a14American journal of physiology. Regulatory, integrative and comparative physiology · 2018
    Article
  6. 20-HETE: Hypertension and Beyond.Hypertension (Dallas, Tex. : 1979) · 2018
    Review
  7. Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction.American journal of physiology. Heart and circulatory physiology · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Molecular determinants of acute kidney injury.Journal of injury & violence research · 2015
    Review
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Guangrui LaiDepartment of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, Peoples Republic of China.
Jingjing Wu
Xiaoliang Liu
Yanyan Zhao
China Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Signal TransductionAmidinesAnimalsBlood GlucoseCell LineCyclic AMPCyclic AMP-Dependent Protein KinasesCytochrome P-450 Enzyme SystemGlucose Transporter Type 1Glycogen PhosphorylaseHydroxyeicosatetraenoic AcidsHyperglycemiaHypertensionInsulin Receptor Substrate ProteinsIsoquinolinesLiver20-hydroxy-5,8,11,14-eicosatetraenoic acidAmidinesBlood GlucoseCyclic AMPCyclic AMP-Dependent Protein KinasesCytochrome P-450 Enzyme SystemGlucose Transporter Type 1Glycogen PhosphorylaseHET0016Hydroxyeicosatetraenoic AcidsInsulin Receptor Substrate ProteinsIrs1 protein, mouseIsoquinolinesN-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamidePhosphorylase KinaseSlc2a1 protein, mouseSulfonamides

Identifiers

PMID22918876
PMCPMC5416963
OpenAlexW2062438062

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.