Antidiabetic Effects of miR-337-3p on Type 2 Diabetes Mellitus Mice by Regulating the DRD1/JAK/STAT Pathway

RuiQiong Ke, Yan Wang, ShiHua Hong, LiXia Xiao

Article ID: 7452
Vol 37, Issue 8, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233708.396
Received: 8 September 2023; Accepted: 8 September 2023; Available online: 8 September 2023; Issue release: 8 September 2023

Abstract

Background: Type 2 diabetes mellitus (T2DM) is mainly caused by glucose and lipid metabolism disorder. Understanding the molecular mechanisms of metabolic disorders is crucial for treating T2DM. This study investigated the effects of miR-337-3p on glycolipid metabolism in T2DM mice by targeting Dopamine receptor D1 (DRD1) expression and activating the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Methods: A T2DM mouse model was established by feeding C57BL/6 mice with high-fat diet and peritoneal injection of streptozotocin. miR-337-3p and DRD1 messenger RNA (mRNA) in T2DM mice were checked by the reverse transcription-qualitative polymerase chain reaction (RT-qPCR) method. The DRD1 protein and JAK/STAT expression were analyzed by Western blot. Lipid accumulation in liver tissue was determined by oil red O staining. Blood glucose, blood lipids, and liver glycogen levels were measured. Finally, the targeting relationship between miR-337-3p and DRD1 was studied via dual luciferase reporter assay. Results: Experimental data supported that miR-337-3p was downregulated in T2DM mice, while DRD1 was upregulated. Overexpressing miR-337-3p can reduce blood glucose and lipid levels, increase hepatic glycogen content, and reduce hepatic lipid accumulation in T2DM mice. DRD1 was targeted by miR-337-3p and could regulate the JAK/STAT pathway. Downregulating DRD1 has a healing effect on T2DM mice by reducing glucose and lipid metabolism. Furthermore, upregulating DRD1 abolishes the effect of upregulating miR-337-3p in T2DM mice. Conclusions: miR-337-3p is a key modifier of hepatic glucose and lipid metabolism and an activator of the JAK/STAT pathway by targeting DRD1, thereby exerting anti-diabetic effects in T2DM mice.


Keywords

miR-337-3p;DRD1;JAK/STAT pathway;type 2 diabetes;glucose and lipid metabolism


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