Evidence map›Paper›PMID 38159884›Full record

ArticleMolecular metabolism2024

Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice.

Antwi-Boasiako Oteng, Srinivas Pittala, Andrea Kliewer, Yishu Qiu, Jürgen Wess

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Review
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

5 authors at 2 institutions in 2 countries.

Antwi-Boasiako OtengMolecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Electronic address: antwi.oteng@nih.gov.
Srinivas PittalaMolecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Andrea KliewerInstitute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
Yishu QiuMolecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Jürgen WessMolecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Electronic address: jurgenw@niddk.nih.gov.
National Institute of Diabetes and Digestive and Kidney Diseases · USJena University Hospital · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveG-protein-coupled receptor (GPCR) kinases (GRKs) abrogate GPCR signaling by promoting receptor desensitization and internalization. Accumulating evidence suggests that GRK2 represents an important regulator of GPCR-mediated effects on systemic glucose metabolism, obesity, and insulin resistance. Despite the key role of the liver in maintaining euglycemia, the potential metabolic relevance of hepatic GRK2 has yet to be examined. Thus, the goal of this study was to explore the potential role of hepatic GRK2 in maintaining glucose homeostasis and other key metabolic functions.

methodsTo address this question, we generated mice that showed a ∼90% reduction in GRK2 protein expression selectively in hepatocytes (Hep-GRK2-KO mice) and subjected these mice, together with their control littermates, to systematic metabolic phenotyping studies.

resultsWe found that Hep-GRK2-KO mice maintained on regular chow did not differ significantly from their control littermates in glycemia, glucose tolerance, insulin sensitivity, in vivo gluconeogenesis, and glucagon-induced hyperglycemia. We obtained similar findings when we analyzed Hep-GRK2-KO mice and control littermates consuming an obesogenic high-fat diet. Likewise, plasma levels of insulin, glucagon, free fatty acids, and ketone bodies remained unaffected by the lack of hepatocyte GRK2. The same was true when we examined the expression levels of key genes regulating hepatic glucose and fatty acid metabolism.

conclusionIn summary, our data suggest that hepatocyte GRK2 is dispensable for systemic glucose homeostasis and other key metabolic functions in both lean and obese mice. This finding suggests that drug development efforts aimed at inhibiting GRK2 to improve impaired glucose homeostasis and insulin sensitivity need to focus on other metabolically important tissues.

Indexed as

Insulin ResistanceAnimalsGlucagonGlucoseG-Protein-Coupled Receptor Kinase 2HomeostasisLiverMiceGlucagonGlucoseG-Protein-Coupled Receptor Kinase 2GRK2 protein, mouseGlucose toleranceG protein-coupled receptorKnockout miceLiverMetabolism

Identifiers

PMID38159884
PMCPMC10809122
OpenAlexW4390350940

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.