Evidence map›Paper›PMID 42565824›Full record

ArticleDiabetologia2026

A GLP-1 receptor agonist enhances islet microvascular flow through nitric oxide-dependent mechanisms in a diabetic mouse model: investigation using intravital two-photon imaging.

Tomohiko Kimura, Kengo Kidokoro, Yuichiro Iwamoto, Hideyuki Iwamoto, Toshitomo Sugisaki, Takashi Itoh, Yoshiro Fushimi, Junpei Sanada, Masashi Shimoda, Shuhei Nakanishi and 3 more

Abstract read
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Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Tomohiko KimuraDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan. tomohiko@med.kawasaki-m.ac.jp.
Kengo KidokoroDepartment of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Yuichiro IwamotoDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Hideyuki IwamotoDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Toshitomo SugisakiDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Takashi ItohDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Yoshiro FushimiDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Junpei SanadaDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Masashi ShimodaDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Shuhei NakanishiDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Kohei KakuDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Naoki KashiharaDepartment of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Hideaki KanetoDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan.

Funding

Japan Diabetes Foundation apan Diabetes Foundation-Sanofi Research GrantJapan Society for the Promotion of Science 21K16360
6 · The paper itself

Abstract

aims/hypothesisImpaired regulation of islet microvascular blood flow has been implicated in beta cell dysfunction in diabetes; this dysregulation is linked to endothelial dysfunction with reduced nitric oxide bioavailability. However, dynamic regulation of islet microvascular flow has not been directly examined in vivo. We hypothesised that acute pharmacological activation of the glucagon-like peptide-1 receptor (GLP-1R) rapidly enhances islet microvascular flow through NO-dependent mechanisms under diabetic conditions.

methodsIslet microvascular dynamics were visualised in vivo using intravital two-photon microscopy in mice with hyperglycaemia induced by multiple low doses of streptozocin (STZ), which represents a model of beta cell dysfunction, and in normoglycaemic controls. Acute vascular responses to the GLP-1R agonist liraglutide were quantified by measuring peri-islet vascular volume fraction and erythrocyte velocity, with or without inhibition of nitric oxide synthase using Nω-nitro-L-arginine methyl ester (L-NAME). To assess the physiological relevance of the results, a subset of diabetic mice received chronic liraglutide treatment, followed by analyses of islet hypoxia and beta cell function.

resultsAcute liraglutide administration in the diabetic mice rapidly increased peri-islet vascular volume fraction (p=0.010) and erythrocyte velocity (p=0.003). These vascular responses were completely abolished by treatment with L-NAME, and were absent in normoglycaemic mice, indicating a diabetes-specific, NO-dependent microvascular response. Chronic liraglutide treatment was associated with reduced islet hypoxia and improved glucose-stimulated insulin secretion (p=0.042), supporting the physiological relevance of acute microvascular enhancement. CONCLUSIONS/

interpretationAcute pharmacological activation of the GLP-1R rapidly enhances NO-dependent islet microvascular flow specifically under diabetic conditions. This previously unrecognised in vivo vascular response indicates dynamic regulation of the islet microenvironment by GLP-1R signalling, and suggests that rapid microvascular adaptation may contribute to preservation of beta cell function during metabolic stress.

Indexed as

Beta cellGLP-1 receptorGLP-1 receptor agonistIn vivo imagingIslet microvascular flowNitric oxide

Identifiers

PMID42565824

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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.