ArticleHepatology (Baltimore, Md.)2011
Genetic ablation or chemical inhibition of phosphatidylcholine transfer protein attenuates diet-induced hepatic glucose production.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease.Molecular metabolism · 2023Article
- STARD3: A Prospective Target for Cancer Therapy.Cancers · 2021Review
- Thioesterase-mediated control of cellular calcium homeostasis enables hepatic ER stress.The Journal of clinical investigation · 2018Article
- Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Deactivating Fatty Acids: Acyl-CoA Thioesterase-Mediated Control of Lipid Metabolism.Trends in endocrinology and metabolism: TEM · 2017Review
- Identification of a functional genetic variant driving racially dimorphic platelet gene expression of the thrombin receptor regulator, PCTP.Thrombosis and haemostasis · 2017Article
- Genetic ablation of phosphatidylcholine transfer protein/StarD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure.Metabolism: clinical and experimental · 2017Article
- Thioesterase superfamily member 2 (Them2) and phosphatidylcholine transfer protein (PC-TP) interact to promote fatty acid oxidation and control glucose utilization.Molecular and cellular biology · 2014Article
- Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c.Nature medicine · 2013Article
- Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.Science signaling · 2013Article
- The Lipid Transfer Protein StarD7: Structure, Function, and Regulation.International journal of molecular sciences · 2013Article
- New players on the metabolic stage: How do you like Them Acots?Adipocyte · 2013Article
- Thioesterase superfamily member 2/acyl-CoA thioesterase 13 (Them2/Acot13) regulates hepatic lipid and glucose metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledPhosphatidylcholine transfer protein (PC-TP, synonym StARD2) is a highly specific intracellular lipid binding protein that is enriched in liver. Coding region polymorphisms in both humans and mice appear to confer protection against measures of insulin resistance. The current study was designed to test the hypotheses that Pctp-/- mice are protected against diet-induced increases in hepatic glucose production and that small molecule inhibition of PC-TP recapitulates this phenotype. Pctp-/- and wildtype mice were subjected to high-fat feeding and rates of hepatic glucose production and glucose clearance were quantified by hyperinsulinemic euglycemic clamp studies and pyruvate tolerance tests. These studies revealed that high-fat diet-induced increases in hepatic glucose production were markedly attenuated in Pctp-/- mice. Small molecule inhibitors of PC-TP were synthesized and their potencies, as well as mechanism of inhibition, were characterized in vitro. An optimized inhibitor was administered to high-fat-fed mice and used to explore effects on insulin signaling in cell culture systems. Small molecule inhibitors bound PC-TP, displaced phosphatidylcholines from the lipid binding site, and increased the thermal stability of the protein. Administration of the optimized inhibitor to wildtype mice attenuated hepatic glucose production associated with high-fat feeding, but had no activity in Pctp-/- mice. Indicative of a mechanism for reducing glucose intolerance that is distinct from commonly utilized insulin-sensitizing agents, the inhibitor promoted insulin-independent phosphorylation of key insulin signaling molecules.
conclusionThese findings suggest PC-TP inhibition as a novel therapeutic strategy in the management of hepatic insulin resistance.
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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.