Evidence map›Paper›PMID 31867105›Full record

ArticleCancer & metabolism2019

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

Ali R Nasiri, Marcos R Rodrigues, Zongyu Li, Brooks P Leitner, Rachel J Perry

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

Article in Cancer & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 4 pooled it
3.3field-weighted citation impact, top 7% 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

78 citing papers in PubMed, 4 syntheses or guidelines pooled it, 111 citations in OpenAlex.

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18 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

5 authors at 1 institution in 2 countries.

Ali R Nasiri1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.
Marcos R Rodrigues1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.
Zongyu Li1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.
Brooks P Leitner1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.
Rachel J Perry1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.ORCID 0000-0003-0748-8064
Yale University · US

Funding

Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Richard A Flavell · 1993 to 2026
$44.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Regulation of tumor growth and metabolism by hyperinsulinemiaR00CA215315 · NCI · YALE UNIVERSITY · PI PERRY, RACHEL JAMISON · 2018 to 2020
$689k
Regulation of tumor growth and metabolism by hyperinsulinemiaK99CA215315 · NCI · YALE UNIVERSITY · PI PERRY, RACHEL JAMISON · 2017 to 2018
$297k
NCI NIH HHS K99 CA215315NCI NIH HHS R00 CA215315NIDDK NIH HHS P30 DK045735NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

backgroundObesity confers an increased risk and accelerates the progression of multiple tumor types in rodents and humans, including both breast and colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, and mechanistic insights as to the obesity-cancer connection have been lacking.

methodsE0771 breast tumors and MC38 colon tumors were treated in vivo in mice and in vitro with two mechanistically different insulin-lowering agents, a controlled-release mitochondrial protonophore (CRMP) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, and tumor growth and glucose metabolism were assessed. Groups were compared by ANOVA with Bonferroni's multiple comparisons test.

resultsDapagliflozin slows tumor growth in two mouse models (E0771 breast cancer and MC38 colon adenocarcinoma) of obesity-associated cancers in vivo, and a mechanistically different insulin-lowering agent, CRMP, also slowed breast tumor growth through its effect to reverse hyperinsulinemia. In both models and with both agents, tumor glucose uptake and oxidation were not constitutively high, but were hormone-responsive. Restoration of hyperinsulinemia by subcutaneous insulin infusion abrogated the effects of both dapagliflozin and CRMP to slow tumor growth.

conclusionsTaken together, these data demonstrate that hyperinsulinemia per se promotes both breast and colon cancer progression in obese mice, and highlight SGLT2 inhibitors as a clinically available means of slowing obesity-associated tumor growth due to their glucose- and insulin-lowering effects.

Indexed as

GlucoseInsulinObesityTumor metabolism

Identifiers

PMID31867105
PMCPMC6907191
OpenAlexW2996729736

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.