Diacylglycerol kinase δ functions as a proliferation suppressor in pancreatic ß-cells.
FASEB J
; 35(5): e21420, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33774855
Although an aberrant reduction in pancreatic ß-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of ß-cell mass is poorly understood. Here, we show that diacylglycerol kinase δ (DGKδ) is a key enzyme in the regulation of ß-cell mass. DGKδ expression was detected in the nucleus of ß-cells. We developed ß-cell-specific DGKδ knockout (ßDGKδ KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of ßDGKδ KO mice. DGKδ knockdown in the ß-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and ß-cell loss were alleviated in ßDGKδ KO mice. Thus, suppressing the expression or enzymatic activity of DGKδ that functions as a suppressor of ß-cell proliferation could be a novel therapeutic approach to increase ß-cell mass for the treatment of diabetes.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Diacilglicerol Quinasa
/
Proliferación Celular
/
Diabetes Mellitus Experimental
/
Células Secretoras de Insulina
/
Hiperglucemia
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón