Loss of miR-23b/27b/24-1 Cluster Impairs Glucose Tolerance via Glycolysis Pathway in Mice

Autor: Han Zhao, Jia-Lin Li, Huang-Cong Shi, Yonghui Jiang, Yue Liu, Chang-Jian Yin, Shigang Zhao, Yuanyuan Man
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
T2DM
030209 endocrinology & metabolism
Nicotinamide adenine dinucleotide
Phosphoenolpyruvic acid
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Respiratory Rate
Downregulation and upregulation
miR-23b/27b/24-1 cluster
Glucose Intolerance
Animals
Humans
Glucose homeostasis
Glycolysis
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Mice
Knockout
Chemistry
Organic Chemistry
General Medicine
Metabolism
glycolysis
NAD
Molecular biology
Computer Science Applications
MicroRNAs
Glucose
030104 developmental biology
impaired glucose tolerance
Diabetes Mellitus
Type 2
lcsh:Biology (General)
lcsh:QD1-999
Multigene Family
NAD+ kinase
Pyruvate kinase
Signal Transduction
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 2
International Journal of Molecular Sciences, Vol 22, Iss 550, p 550 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22020550
Popis: Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje