Evidence map›Paper›PMID 21454710›Full record

ArticleThe Journal of biological chemistry2011

Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets.

Michael J MacDonald, Melissa J Longacre, Scott W Stoker, Mindy Kendrick, Ansaya Thonpho, Laura J Brown, Noaman M Hasan, Sarawut Jitrapakdee, Toshiyuki Fukao, Matthew S Hanson and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
7.7field-weighted citation impact, top 3% 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

56 citing papers in PubMed, 99 citations in OpenAlex.

  1. Trial
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  7. Article
  8. Review
  9. Review
  10. Understanding the Structural Arrangement of Islets in Chronic Pancreatitis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
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  18. Persistent organic pollutants and β-cell toxicity: a comprehensive review.American journal of physiology. Endocrinology and metabolism · 2022
    Review
  19. Review
  20. 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

12 authors at 3 institutions in 3 countries.

Michael J MacDonaldDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA. mjmacdon@wisc.edu
Melissa J Longacre
Scott W Stoker
Mindy Kendrick
Ansaya Thonpho
Laura J Brown
Noaman M Hasan
Sarawut Jitrapakdee
Toshiyuki Fukao
Matthew S Hanson
Luis A Fernandez
Jon Odorico
University of Wisconsin–Madison · USGifu University · JPMahidol University · TH

Funding

GLUCOSE/SECRETAGOGUE METABOLISM IN PANCREATIC ISLETSR01DK028348 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MACDONALD, MICHAEL JOHN · 1986 to 2013
$7.0M
GLUCOSE/SECRETAGOGUE METABOLISM IN PANCREATIC ISLETSR55DK028348 · NIDDK · UNIVERSITY OF WISCONSIN MADISON · PI MACDONALD, MICHAEL JOHN · 1992 to 1992
–
NIDDK NIH HHS DK28348NIDDK NIH HHS R01 DK028348
6 · The paper itself

Abstract

Anaplerosis, the net synthesis in mitochondria of citric acid cycle intermediates, and cataplerosis, their export to the cytosol, have been shown to be important for insulin secretion in rodent beta cells. However, human islets may be different. We observed that the enzyme activity, protein level, and relative mRNA level of the key anaplerotic enzyme pyruvate carboxylase (PC) were 80-90% lower in human pancreatic islets compared with islets of rats and mice and the rat insulinoma cell line INS-1 832/13. Activity and protein of ATP citrate lyase, which uses anaplerotic products in the cytosol, were 60-75% lower in human islets than in rodent islets or the cell line. In line with the lower PC, the percentage of glucose-derived pyruvate that entered mitochondrial metabolism via carboxylation in human islets was only 20-30% that in rat islets. This suggests human islets depend less on pyruvate carboxylation than rodent models that were used to establish the role of PC in insulin secretion. Human islets possessed high levels of succinyl-CoA:3-ketoacid-CoA transferase, an enzyme that forms acetoacetate in the mitochondria, and acetoacetyl-CoA synthetase, which uses acetoacetate to form acyl-CoAs in the cytosol. Glucose-stimulated human islets released insulin similarly to rat islets but formed much more acetoacetate. β-Hydroxybutyrate augmented insulin secretion in human islets. This information supports previous data that indicate beta cells can use a pathway involving succinyl-CoA:3-ketoacid-CoA transferase and acetoacetyl-CoA synthetase to synthesize and use acetoacetate and suggests human islets may use this pathway more than PC and citrate to form cytosolic acyl-CoAs.

Indexed as

AcetoacetatesAnimalsATP Citrate (pro-S)-LyaseCell Line, TumorGlucoseHumansIslets of LangerhansMicePyruvate CarboxylasePyruvic AcidRatsRats, Sprague-DawleySpecies SpecificitySweetening AgentsAcetoacetatesacetoacetic acidATP Citrate (pro-S)-LyaseGlucosePyruvate CarboxylasePyruvic AcidSweetening Agents

Identifiers

PMID21454710
PMCPMC3099655
OpenAlexW1969165259

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.