Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity.
Sci Rep
; 12(1): 11969, 2022 07 13.
Article
en En
| MEDLINE
| ID: mdl-35831364
ABSTRACT
Abnormal microRNA functions are closely associated with pancreatic ß-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 ß-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in ß-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected ß-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 ß-cell dysfunction. In addition, loss of ß-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 ß-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 ß-cell identity and function.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Glucagón
/
Células Secretoras de Insulina
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos