Evidence map›Paper›PMID 41345649›Full record

ArticleCell communication and signaling : CCS2025

Loss of melatonin signaling increases the risk of T2DM caused by metabolic disorders.

Laiqing Yan, Dongying Lv, Lu Zhang, Yu Gao, Tianqi Zhu, Meng Ding, Yujun Yao, Haixin Wu, Yao Fu, Guangdong Li and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

17 authors.

Laiqing Yan *State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Dongying Lv *State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Lu Zhang *State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Yu GaoState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Tianqi ZhuState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Meng DingDepartment of Reproductive Medicine, Zhuozhou Hospital of Hebei Province, Zhuozhou, 072750, China.
Yujun YaoState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Haixin WuState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Yao FuState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Guangdong LiState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Pengyun JiState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Likai WangState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Huigang HanState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Yunjie LiuState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Ana Coto-MontesDepartamento de Morfología y Biología Celular, Julián Clavería, University of Oviedo, Oviedo, 33006, Spain.
Rüdiger HardelandJohann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, 37073, Göttingen, Germany.
Guoshi LiuState Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding（MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China. gshliu@cau.edu.cn.

Funding

National Natural Science Foundation of China (32172733, 32430101 and 32202673)
6 · The paper itself

Abstract

Type 2 diabetes mellitus (T2DM) poses a significant global health challenge. Genome-wide Association Studies have linked T2DM to genetic variants in the melatonin receptor 1a (MTNR1A) and 1b (MTNR1B) genes, which encode the MT1 and MT2 receptors, respectively. Our results found that the rs2119882 MT1 mutation was associated with higher blood glucose levels and increased body mass index (BMI) in humans. Metabolomic analysis showed elevated levels of palmitic acid (a saturated fatty acid) and reduced levels of oleic acid (an unsaturated fatty acid) in individuals with this mutation. In contrast, the rs10830963 MT2 mutation did not show the significant differences in blood glucose level or BMI compared to normal control individuals. Inhibition of MTNR1A and MTNR1B expression led to lower GLUT-4 mRNA and insulin receptor protein levels in human liver cells, resulting in decreased glycogen synthesis and metabolic disruptions. We used CRISPR/Cas9 to create MTNR1A and MTNR1B knockout (KO) mice, which also exhibited reduced GLUT-4 and INSR mRNA levels, decreased glucose tolerance, and increased insulin resistance. These mice also developed obesity, liver lipid deposition, increased abdominal white adipose tissue, and lower androgen levels. Metabolomic and proteomic analyses of the KO mice revealed increased triglycerides and phospholipids, and decreased unsaturated fatty acids. Proteomic studies showed reduced levels of insulin receptor tyrosine kinase, lipid droplet-associated hydrolase, and glucose-6-phosphate dehydrogenase, disrupting fatty acid metabolism and increasing liver lipid deposition. Additionally, a high-fat diet challenge in MTNR1A and MTNR1B KO male mice accelerate the INSR protein expression suppression, hepatic triglyceride accumulation, blood glucose elevation and weight gain. Finally, we generated AANAT over-expressing sheep, which showed improved glucose tolerance and higher insulin levels after glucose injection compared to WT sheep. These findings underscore the importance of melatonin and its receptors in glucose and lipid metabolism, suggesting their deficiencies may contribute to T2DM.

Indexed as

Diabetes Mellitus, Type 2MelatoninReceptor, Melatonin, MT1Signal TransductionAnimalsGlucose Transporter Type 4HumansMaleMiceMice, KnockoutReceptor, InsulinReceptor, Melatonin, MT2Risk FactorsGlucose Transporter Type 4MelatoninMTNR1A protein, humanMTNR1B protein, humanReceptor, InsulinReceptor, Melatonin, MT1Receptor, Melatonin, MT2Blood glucoseInsulinMelatoninMelatonin receptorMetabolic disordersT2DM

Identifiers

PMID41345649
PMCPMC12781753

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.