15 January 2020 : Animal Research
Interaction of Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) and Liver Linase B1 (LKB1) Mitigates Type 2 Diabetes Mellitus by Activating Monophosphate-Activated Protein Kinase (AMPK)/Sirtuin 1 (SIRT1) Axis and Inhibiting Nuclear Factor-kappa B (NF-κB) Activation
Yi Ming1ACF, Youmin Yin1BCF, Zhaoli Sun1E*DOI: 10.12659/MSM.920278
Med Sci Monit 2020; 26:e920278
Abstract
BACKGROUND: Nuclear receptor subfamily 4 group A member 1 (Nr4a1) has been increasingly investigated in association with type 2 diabetes mellitus (T2DM). This study aimed to explore its efficacy with liver kinase B1 (LKB1) and potential signaling pathways in T2DM.
MATERIAL AND METHODS: A T2DM model in rats was established by high-fat diet and injection of 30 mg/kg streptozotocin. The ectopic expression of Nr4a1 or in combination with LKB1 was performed in T2DM rats to probe their effects on T2DM. Then, the weight and indicators of blood lipid and blood glucose in normal rats and T2DM rats were measured. The volume change of adipocytes and the size of lipid droplets in white adipose tissue (WAT) were observed by hematoxylin-eosin staining and oil red O staining, respectively. We also measured levels of Nr4a1, LKB1, and adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/Nuclear factor-kappa B (NF-κB) axis-related proteins.
RESULTS: In T2DM rats, Nr4a1 was highly expressed, and body weight, blood lipid and blood glucose were increased, and the volume of adipocytes and the size of lipid droplets in WAT were increased, which were all reversed by low expression of Nr4a1. After treatment with Nr4a1 and LKB1 together, T2DM rats showed decreased levels of blood lipid, blood glucose, and reduced volume of adipocytes and lipid droplet size in WAT, with activated AMPK/SIRT1 signaling pathway and inhibited NF-κB.
CONCLUSIONS: Our results highlight that interaction of Nr4a1 and LKB1 can mitigate T2DM by activating the AMPK/SIRT1 signaling pathway and inhibiting NF-κB activation. This may offer new insight for T2DM treatment.
Keywords: Adipose Tissue, White, Diabetes Mellitus, Type 2, Nuclear Receptor Subfamily 4, Group A, Member 1, AMP-Activated Protein Kinase Kinases, AMP-Activated Protein Kinases, Blood Glucose, Gene Silencing, Lipids, Protein Binding, Protein Serine-Threonine Kinases, RNA, Messenger, Sirtuin 1
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
26 Feb 2024 : Clinical Research
Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in...Med Sci Monit In Press; DOI: 10.12659/MSM.942509
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952