Evidence mapPaperPMID 30160993Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2018

Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes.

Leslie R Sedgeman, Carine Beysen, Ryan M Allen, Marisol A Ramirez Solano, Scott M Turner, Kasey C Vickers

Open access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  6. Article
  7. Bile acids and microbes in metabolic disease.World journal of gastroenterology · 2022
    Review
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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

6 authors at 3 institutions in 1 country.

Leslie R SedgemanDepartment of Molecular Physiology and Biophysics, Vanderbilt University , Nashville, Tennessee.
Carine BeysenKineMed, Incorporated, Emeryville, California.
Ryan M AllenDepartment of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.
Marisol A Ramirez SolanoDepartment of Biostatistics, Vanderbilt University Medical Center , Nashville, Tennessee.
Scott M TurnerKineMed, Incorporated, Emeryville, California.
Kasey C VickersDepartment of Molecular Physiology and Biophysics, Vanderbilt University , Nashville, Tennessee.ORCID 0000-0001-5643-3102
KineMed (United States) · USVanderbilt University · USVanderbilt University Medical Center · US

Funding

Non-Coding RNA Analytical CoreP01HL116263 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 to 2025
$17.7M
Vanderbilt/Meharry Initiative for Minority Student DvptR25GM062459 · VANDERBILT UNIVERSITY · 2002 to 2005
$2.2M
PHARMACOLOGY AND PHYSIOLOGY OF CARDIOVASCULAR DISEASEST32HL007411 · VANDERBILT UNIVERSITY · 1985 to 2005
$1.7M
NHLBI NIH HHS K22 HL113039NHLBI NIH HHS P01 HL116263NHLBI NIH HHS R01 HL127173NHLBI NIH HHS R01 HL128996NHLBI NIH HHS T32 HL007411NIGMS NIH HHS R25 GM062459
6 · The paper itself

Abstract

Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose-lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNAs (miRNAs) as regulators of metabolic disease and to investigate the link between the cholesterol and glucose-lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker diabetic fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared with vehicle controls. Inhibition of miR-182 in vivo attenuated colesevelam-mediated improvements to glycemic control in db/db mice. Hepatic expression of mediator complex subunit 1 (MED1), a nuclear receptor coactivator, was significantly decreased with colesevelam treatments in db/db mice, and MED1 was experimentally validated to be a direct target of miR-96/182/183 in humans and mice. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-182-5p, a mechanism that directly links cholesterol and glucose metabolism. NEW & NOTEWORTHY Colesevelam lowers systemic glucose levels in Zucker diabetic fatty rats and db/db mice and increases hepatic levels of the sterol response element binding protein 2-responsive microRNA cluster miR-96/182/183. Inhibition of miR-182 in vivo reverses the glucose-lowering effects of colesevelam in db/db mice. Mediator complex subunit 1 (MED1) is a novel, direct target of the miR-96/182/183 cluster in mice and humans.

Indexed as

AnimalsAnticholesteremic AgentsBile Acids and SaltsColesevelam HydrochlorideDiabetes Mellitus, Type 2GlucoseGlycolysisHEK293 CellsHumansHypoglycemic AgentsIntestinal MucosaLiverMaleMediator Complex Subunit 1MicroRNAsRatsAnticholesteremic AgentsBile Acids and SaltsColesevelam HydrochlorideGlucoseHypoglycemic AgentsMed1 protein, ratMediator Complex Subunit 1MicroRNAsMIRN182 microRNA, ratbile acid sequestrantscholesterolglucose metabolismmicroRNAssterol-regulatory element binding protein 2

Identifiers

PMID30160993
PMCPMC6415711
OpenAlexW2889415388

What Socratic 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 Socratic graph.