MicroRNA Dysregulation in Liver and Pancreas of CMP-Neu5Ac Hydroxylase Null Mice Disrupts Insulin/PI3K-AKT Signaling

Abstract

CMP-Neu5Ac hydroxylase (Cmah)-null mice fed with a high-fat diet develop fasting hyperglycemia, glucose intolerance, and pancreatic β-cell dysfunction and ultimately develop characteristics of type 2 diabetes. The precise metabolic role of the Cmah gene remains poorly understood. This study was designed to investigate the molecular mechanisms through which microRNAs (miRNAs) regulate type 2 diabetes. Expression profiles of miRNAs in Cmah-null mouse livers were compared to those of control mouse livers. Liver miFinder miRNA PCR arrays (n = 6) showed that eight miRNA genes were differentially expressed between the two groups. Compared with controls, seven miRNAs were upregulated and one miRNA was downregulated in Cmah-null mice. Specifically, miR-155-5p, miR-425-5p, miR-15a-5p, miR-503-5p, miR-16-5p, miR-29a-3p, and miR-29b-3p were significantly upregulated in the liver and pancreas of Cmah-null mice. These target miRNAs are closely associated with dysregulation of insulin/PI3K-AKT signaling, suggesting that the Cmah-null mice could be a useful model for studying diabetes.

MicroRNA-16 modulates macrophage polarization leading to improved insulin sensitivity in myoblasts

“…Bcl2, an anti-apoptotic protein, is also reported to associate directly with insulin receptor substrates (IRS1/2), which has the potential to alter the insulin signaling [78]. Further Kwon et al proposed that miR-16 may have a role to play in insulin/PI3k-Akt signaling cascade [79]. Taken together, our findings demonstrate that miR- Values were normalized with U6 and expressed relative to control diet which was set as 1.…”

Jiang Tang Xiao Ke Granule Protects Hepatic Tissue of Diabetic Mice Through Modulation of Insulin and Ras Signaling – A Bioinformatics Analysis of MicroRNAs and mRNAs Network

“…In addition, miR-425 has been shown to be upregulated in liver tissue of HFD-induced obese mice. On the one hand, mir-425 impairs insulin/PI3K/AKT signal transduction; on the other hand, this miRNA is actively involved in the inflammatory response mediated by NF-κB (Kwon et al, 2014;Arora et al, 2016). MiR-214 had been demonstrated to aggravate insulin resistance by inhibiting Akt and Rock1 expression, which indicated its negative impact on insulin signaling (Honardoost et al, 2018).…”

Plasma microRNA‐16‐5p, ‐17‐5p and ‐20a‐5p: Novel diagnostic biomarkers for gestational diabetes mellitus

“…In addition, miR-16-5p was significantly upregulated in the liver and pancreas of CMP-Neu5Ac hydroxylase (Cmah)-null mice, which ultimately developed type 2 diabetes. 38 Also, macrophage-conditioned media (MCM) from diabetes mellitus decreased the expression of p21 Cip1 and p27 Kip1 , increased the expression of miR-17-5p and induced smooth muscle cell proliferation, indicating that miR-17-5p plays a critical role in vascular complications in DM patients. 39 For microRNA-20a-5p, there has been no relevant study on type 2 diabetes and other metabolic disease.…”