Evidence map›Paper›PMID 28666119›Full record

ArticleCell2017

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.

Victor Rusu, Eitan Hoch, Josep M Mercader, Danielle E Tenen, Melissa Gymrek, Christina R Hartigan, Michael DeRan, Marcin von Grotthuss, Pierre Fontanillas, Alexandra Spooner and 20 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07760883 (Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status), which is not on this map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
20.1field-weighted citation impact, top 1% 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.

NCT07760883 recruitingnot on this mapstarted 2020, after this paper: background citation

Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status

TypeobservationalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2020 to 2027Enrolled154ConditionsDiabetes Type 2
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. CD147/Basigin: From Integrative Molecular Hub to Translational Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Admixture Mapping of Lipid Traits in Hispanic Americans.Journal of the American Heart Association · 2025
    Article
  13. Phenotypic and Genetic Diversity in Diabetes Across Populations.The Journal of clinical endocrinology and metabolism · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 5 institutions in 3 countries.

Victor RusuProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Eitan HochProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Metabolism Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Josep M MercaderProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Barcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, 08034 Barcelona, Spain.
Danielle E TenenBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Melissa GymrekProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Christina R HartiganBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Michael DeRanBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Marcin von GrotthussProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Pierre FontanillasProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Alexandra SpoonerProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Gaelen GuzmanBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Amy A DeikBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Kerry A PierceBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Courtney DennisBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Clary B ClishMetabolism Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Steven A CarrBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Bridget K WagnerBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Monica SchenoneBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Maggie C Y NgCenter for Genomics and Personalized Medicine Research, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Brian H ChenLongitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
MEDIA Consortium
SIGMA T2D Consortium
Federico Centeno-CruzInstituto Nacional de Medicina Genómica, Tlalpan, 14610 Mexico City, Mexico.
Carlos ZerrweckThe Obesity Clinic at Hospital General Tlahuac, 13250 Mexico City, Mexico.
Lorena OrozcoInstituto Nacional de Medicina Genómica, Tlalpan, 14610 Mexico City, Mexico.
David M AltshulerProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
Stuart L SchreiberBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jose C FlorezProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Metabolism Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jcflorez@mgh.harvard.edu.
Suzanne B R JacobsProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Metabolism Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Eric S LanderBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lander@broadinstitute.org.
Broad Institute · USNational Institutes of Health · USNational Institute of Genomic Medicine · MXHospital General de México · MXWake Forest University · US

Funding

Center for Common Disease GeneticsUM1HG008895 · NHGRI · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH, GABRIEL, STACEY · 2016 to 2020
$111.2M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Genetics of African American Type 2 DiabetesR01DK066358 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI NG, MAGGIE · 2003 to 2019
$6.2M
NHGRI NIH HHS UM1 HG008895NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R01 DK066358
6 · The paper itself

Abstract

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.

Indexed as

BasiginCell MembraneChromosomes, Human, Pair 17Diabetes Mellitus, Type 2Gene Knockdown TechniquesHaplotypesHepatocytesHeterozygoteHistone CodeHumansLiverModels, MolecularMonocarboxylic Acid TransportersBasiginBSG protein, humanMonocarboxylic Acid TransportersSLC16A11 protein, humandisease mechanismfatty acid metabolismgeneticslipid metabolismMCT11monocarboxylatesprecision medicineSLC16A11solute carrier (SLC)type 2 diabetes (T2D)

Identifiers

PMID28666119
PMCPMC5562285
OpenAlexW2727413563

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.