Evidence mapPaperPMID 39918873Full record

ReviewPhysiological reviews2025

Molecular dissection of the role of ACE2 in glucose homeostasis.

Kavaljit H Chhabra, Robin Shoemaker, Chandana B Herath, Merlin C Thomas, Catalin M Filipeanu, Eric Lazartigues

Abstract readReview
In one paragraph

Review in Physiological reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

  1. Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026
    Review
  2. Review
  3. Genetic Analysis and Clinical Effect ofSultan Qaboos University medical journal · 2026
    Article
  4. Review
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.

Kavaljit H ChhabraDepartment of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, Kentucky, United States.
Robin ShoemakerDepartment of Pediatrics, University of Kentucky, Lexington, Kentucky, United States.ORCID 0000-0002-9972-7677
Chandana B HerathDepartment of Medicine, Melbourne Medical School, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.ORCID 0000-0001-9151-8531
Merlin C ThomasDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0003-0694-8743
Catalin M FilipeanuCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.
Eric LazartiguesCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.ORCID 0000-0001-7290-0786

Funding

Targeting ACE2 ubiquitination for hypertensionR01HL150592 · NHLBI · LSU HEALTH SCIENCES CENTER · PI Eric D Lazartigues · 2022 to 2023
$1.2M
Targeting ADAM17 maturation in resistant hypertension.R01HL163588 · LSU HEALTH SCIENCES CENTER · 2025 to 2025
$549k
Role of Hypothalamic MC4R in Glucose Homeostasis via a Novel Neuroendocrine Circuit involving the Kidneys and Adrenal GlandsR01DK124619 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$337k
BLRD VA I01 BX004294BLRD VA I01 BX005475NHLBI NIH HHS R01 HL150592NHLBI NIH HHS R01 HL163588NHLBI NIH HHS R01 HL163814NIDDK NIH HHS R01 DK124619NIDDK NIH HHS R56 DK140148
6 · The paper itself

Abstract

Angiotensin-converting enzyme 2 (ACE2) was discovered 25 years ago as a negative regulator of the renin-angiotensin system, opposing the effects of angiotensin II. Beyond its well-demonstrated roles in cardiovascular regulation and COVID-19 pathology, ACE2 is involved in a plethora of physiopathological processes. In this review, we summarize the latest discoveries on the role of ACE2 in glucose homeostasis and regulation of metabolism. In the endocrine pancreas, ACE2 is expressed at low levels in β-cells, but loss of its expression inhibits glucose-stimulated insulin secretion and impairs glucose tolerance. Conversely, overexpression of ACE2 improved glycemia, suggesting that recombinant ACE2 might be a future therapy for diabetes. In the skeletal muscle of ACE2-deficient mice a progressive triglyceride accumulation was observed, whereas in diabetic kidney the initial increase in ACE2 is followed by a chronic reduction of expression in kidney tubules and impairment of glucose metabolism. At the intestinal level dysregulation of the enzyme alters the amino acid absorption and intestinal microbiome, whereas at the hepatic level ACE2 protects against diabetic fatty liver disease. Not least, ACE2 is upregulated in adipocytes in response to nutritional stimuli, and administration of recombinant ACE2 decreased body weight and increased thermogenesis. In addition to tissue-specific regulation of ACE2 function, the enzyme undergoes complex cellular posttranslational modifications that are changed during diabetes evolution, with at least proteolytic cleavage and ubiquitination leading to modifications in ACE2 activity. Detailed characterization of ACE2 in a cellular and tissue-specific manner holds promise for improving therapeutic outcomes in diabetes and metabolic disorders.

Indexed as

Angiotensin-Converting Enzyme 2GlucoseHomeostasisAnimalsCOVID-19HumansACE2 protein, humanAngiotensin-Converting Enzyme 2Glucoseangiotensin-converting enzyme 2diabetesglucose homeostasisrenin-angiotensin system

Identifiers

PMID39918873
PMCPMC12124467

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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 Socratic graph.