Evidence map›Paper›PMID 42330303›Full record

ArticleDiabetes2026

β-Hydroxybutyrate Improves Glucose Metabolism in Streptozotocin-Induced Type 1 Diabetes by Inhibiting Gut and Liver Glucose Transporters via GPR109A.

Shaobo Li, Jingjie Wang, Chunxiao Xin, Yiling Dong, Anqi Xie, Jing Song, Jing Wan, Jun Yin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Shaobo LiState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0001-7313-6054
Jingjie WangState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chunxiao XinJiangxi University of Chinese Medicine, Nanchang, China.
Yiling DongState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Anqi XieJiangxi University of Chinese Medicine, Nanchang, China.
Jing SongDepartment of Endocrinology and Metabolism, Shanghai Eighth People's Hospital, Shanghai, China.
Jing WanDepartment of Endocrinology and Metabolism, Shanghai Eighth People's Hospital, Shanghai, China.
Jun YinState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-9826-3583

Funding

National Key Clinical Specialty Z155080000004National Key Research and Development Plan 2023YFF0713705Shanghai Municipal Health Commission Clinical Research Fund 202540071Shanghai Municipal Key Clinical Specialty
6 · The paper itself

Abstract

Ketone bodies, particularly β-hydroxybutyrate (3HB), are often elevated in type 1 diabetes (T1D); however, their physiological roles remain unclear. In a low-carbohydrate diet study, patients with insulin-deficient diabetes exhibited reduced fasting blood glucose and increased fasting blood ketone levels, negatively correlated. Another clinical study using continuous glucose and ketone monitoring confirmed inverse glucose-ketone fluctuations. To test causality, we conducted animal and cellular studies. In streptozotocin-induced T1D mice, 7-week oral 3HB administration improved glucose metabolism and alleviated glycogenic hepatopathy. Imaging with 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography/computed tomography demonstrated reduced hepatic and intestinal glucose uptake. Western blotting confirmed 3HB suppressed glucose transporter (sodium-glucose cotransporter 1, GLUT2, GLUT5) overexpression and normalized glycogen metabolism. In vitro, 3HB dose-dependently inhibited glucose transporter expression and glucose uptake in primary hepatocytes and IEC-6 cells. G protein-coupled receptor 109A (GPR109A) serves as the primary receptor for 3HB. Mechanistic studies using the GPR109A inhibitor mepenzolate bromide, the mTOR inhibitor rapamycin, and siRNA-mediated gene silencing revealed that these effects were GPR109A dependent and linked to inhibition of the PI3K/AKT/mTOR pathway. Overall, this study provides new insights into the role of ketone bodies in T1D, establishing 3HB as a modulator of glucose homeostasis through GPR109A-mediated suppression of glucose transporters in the liver and intestine. ARTICLE HIGHLIGHTS:

Indexed as

3-Hydroxybutyric AcidDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1GlucoseGlucose Transport Proteins, FacilitativeLiverReceptors, G-Protein-CoupledAnimalsGlucose Transporter Type 2MaleMiceRats3-Hydroxybutyric AcidGlucoseGlucose Transporter Type 2Glucose Transport Proteins, FacilitativeHcar2 protein, mouseHcar2 protein, ratReceptors, G-Protein-Coupled

Identifiers

PMID42330303
PMCPMC13291861

What OpenQuestion holds

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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.