Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity
Document Type
Article
Publication Date
7-13-2022
Department
Department of Biological Sciences
Abstract
Abnormal microRNA functions are closely associated with pancreatic β-cell loss and dysfunction in type 2 diabetes. Dysregulation of miR-30d has been reported in the individuals with diabetes. To study how miR-30d affects pancreatic β-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in β-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected β-cell function. Elevated miR-30d at low-level (TgL, 2-fold) had mild effects on signaling pathways and displayed no significant changes to metabolic homeostasis. In contrast, transgenic mice with high-level of miR-30d expression (TgH, 12-fold) exhibited significant diet-induced hyperglycemia and β-cell dysfunction. In addition, loss of β-cell identity was invariably accompanied with increased insulin/glucagon-double positive bihormonal cells and excess plasma glucagon levels. The transcriptomic analysis revealed that miR-30d overexpression inhibited β-cell-enriched gene expression and induced α-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal β-cell identity and function.
Publication Title
Scientific Reports
Recommended Citation
Mao, Y.,
Schoenborn, J.,
Wang, Z.,
Chen, X.,
Matson, K.,
Mohan, R.,
Zhang, S.,
Tang, X.,
Arunagiri, A.,
Arvan, P.,
&
Tang, X.
(2022).
Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity.
Scientific Reports,
12(1).
http://doi.org/10.1038/s41598-022-16174-7
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/16183