Role and mechanism of cyclophilin D in islet β-cell dysfunction in type 2 diabetic mice
- VernacularTitle:亲环素D在2型糖尿病小鼠胰岛β细胞功能损伤中的作用及机制
- Author:
Xiaoyu CHEN
1
;
Xiujuan ZHANG
Author Information
- Keywords: cyclophilin D; nuclear factor-κB; type 2 diabetes; islet β-cell dysfunction; pancreatic and duodenal homeobox-1; mitochondrial respiratory function; oxygen consumption rate; glucose-stimulated insuli secretion
- From: Journal of Clinical Medicine in Practice 2025;29(13):109-115
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the role and mechanism of nuclear factor-κB(NF-κB)/cyclophilin D(CypD)-mediated mitochondrial stress signaling pathway in islet β-cell dysfunction in type 2diabetic(T2DM)mice.Methods Six-week-old CypD gene knockout(CypD-/-)mice and their wild-type(WT)littermates were randomly divided into normal control groups(CypD-/-group and WT group)and diabetic model groups[CypD-/-+high-fat diet(HFD)+streptozotocin(STZ)group and WT+HFD+STZ group],with six mice in each group.The fasting blood glucose,serum insulin,pancreatic insulin levels,glucose-stimulated insulin secretion(GSIS),NF-κB levels,pan-creatic and duodenal homeobox-1(PDX-1)expression levels,and mitochondrial respiratory oxygen consumption rate(OCR)of islet cells were measured in each group.The CypD level in islet β-cells(INS-1 cells)overexpressing NF-κB was detected using recombinant adenovirus infection technology.Results Compared with the WT+HFD+STZ group,the CypD-/-+HFD+STZ group showed sig-nificant decrease in fasting blood glucose levels,significant increase in serum insulin and pancreatic insulin levels(P＜0.001),and PDX-1 expression levels(P＜0.001).The CypD-/-+HFD+STZ group also exhibited significantly elevated GSIS levels(P＜0.001),and enhanced basal respiration,ATP production,maximal respiration,and reserve respiratory capacity of islet cells compared with the WT+HFD+STZ group(P＜0.001 or P＜0.05).The relative expression level of CypD protein in islet β-cells overexpressing NF-κB was significantly higher than that in control cells(P＜0.05).Conclusion CypD-/-can improve fasting blood glucose and insulin levels in T2DM mice,regulate the downregulation of PDX-1 expression,enhance GSIS and mitochondrial respiratory function,and protect islet β-cells.Overexpression of NF-κB can induce the upregulation of CypD expression and play an upstream regulatory role in the NF-κB/CypD-mediated mitochondrial stress signaling pathway.
