Evidence map›Paper›PMID 7971976›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1994

Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships.

Y Lee, H Hirose, M Ohneda, J H Johnson, J D McGarry, R H Unger

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
280citing papers in PubMed, 2 pooled it
12.5field-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.

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

280 citing papers in PubMed, 2 syntheses or guidelines pooled it, 828 citations in OpenAlex.

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  10. The mediating role of remnant cholesterol in the association between obstructive sleep apnea and diabetes: insights from two independent datasets.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
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  19. Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast.Proceedings of the National Academy of Sciences of the United States of America · 2025
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220 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Y LeeCenter for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235.
H Hirose
M Ohneda
J H Johnson
J D McGarry
R H Unger
The University of Texas Southwestern Medical Center · US

Funding

The Glucoregulatory and Liporegulatory Peptide HormonesR01DK002700 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI UNGER, ROGER HAROLD · 1994 to 2008
$2.5M
ROLE OF INFLAMMATORY CYTOKINES IN ISLET CELL DAMAGEP01DK042582 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI LECHAGO, JUAN · 1990 to 1995
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THE GLUCOREGULATORY PEPTIDE HORMONESR37DK002700 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI UNGER, ROGER H. · 1986 to 1993
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NIDDK NIH HHS 1-PO1-DK42582NIDDK NIH HHS DK02700
6 · The paper itself

Abstract

Hyperinsulinemia, loss of glucose-stimulated insulin secretion (GSIS), and peripheral insulin resistance coexist in non-insulin-dependent diabetes mellitus (NIDDM). Because free fatty acids (FFA) can induce these same abnormalities, we studied their role in the pathogenesis of the NIDDM of obese Zucker diabetic fatty (ZDF-drt) rats from 5 weeks of age (before the onset of hyperglycemia) until 14 weeks. Two weeks prior to hyperglycemia, plasma FFA began to rise progressively, averaging 1.9 +/- 0.06 mM at the onset of hyperglycemia (P < 0.001 vs. controls). At this time GSIS was absent and beta-cell GLUT-2 glucose transporter was decreased. The triacylglycerol content of prediabetic islets rose to 10 times that of controls and was correlated with plasma FFA (r = 0.825; P < 0.001), which, in turn, was correlated with the plasma glucose concentration (r = 0.873; P < 0.001). Reduction of hyperlipacidemia to 1.3 +/- 0.07 mM by pair feeding with lean littermates reduced all beta-cell abnormalities and prevented hyperglycemia. Normal rat islets that had been cultured for 7 days in medium containing 2 mM FFA exhibited increased basal insulin secretion at 3 mM glucose, and first-phase GSIS was reduced by 68%; in prediabetic islets, first-phase GSIS was reduced by 69% by FFA. The results suggest a role for hyperlipacidemia in the pathogenesis of NIDDM; resistance to insulin-mediated antilipolysis is invoked to explain the high FFA despite hyperinsulinemia, and sensitivity of beta cells to hyperlipacedemia is invoked to explain the FFA-induced loss of GSIS.

Indexed as

AdipocytesAnimalsDiabetes Mellitus, Type 2Energy IntakeFatty AcidsFatty Acids, NonesterifiedFemaleIslets of LangerhansMaleRatsRats, Mutant StrainsRats, WistarTriglyceridesFatty AcidsFatty Acids, NonesterifiedTriglycerides

Identifiers

PMID7971976
PMCPMC45129
OpenAlexW2065504943

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.