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Title 

The orphan nuclear receptor small heterodimer partner negatively regulates pancreatic beta cell survival and hyperglycemia in multiple low-dose streptozotocin-induced type 1 diabetic mice

Authors 

Jung Ran NohJung Hwan HwangYong Hoon KimKyoung Shim KimGil Tae GangSang Woo KimD K KimM ShongI K LeeH S ChoiChul Ho Lee

Publisher 

Elsevier

Issue Date 

2013

Citation 

International Journal of Biochemistry & Cell Biology, vol. 45, no. 8, pp. 1538-1545

Keywords 

Beta cell apoptosisDiabetesInsulinSmall heterodimer partnerStreptozotocin

Abstract 

The small heterodimer partner (SHP; NR0B2) regulates the transcription of a variety of target genes andcontrols a variety of physiological functions in various tissues. However, the role of SHP in beta cell hasnot been fully determined yet. We used SHP knockout (SHP KO) mice to investigate the role of SHP inmultiple low-dose streptozotocin (MLDS)-induced diabetes. Blood glucose and insulin levels were mea-sured until 20 days, and intraperitoneal glucose tolerance and glucose-stimulated insulin secretion testswere performed. The expression of apoptotic genes and beta cell markers were detected by quantitative realtime-polymerase chain reaction, immunostaining and western blot analysis. SHP KO mice showed significantly lower blood glucose, higher insulin levels, and enhanced glucose tolerance compared with wild type (WT) mice after MLDS treatment. Moreover, beta cell mass and pancreatic insulin contentwere remarkably increased in SHP KO mice. In the response to glucose stimulation, islets of SHP KO showed increased insulin secretion via up-regulation of beta cell enriched transcription factors com-pared to WT mice after streptozotocin (STZ) treatment. In quantification for beta cell apoptosis at day 1post STZ treatment, the SHP KO mice showed significantly increased anti-apoptotic gene expression anddecreased release of apoptotic markers cytochrome c, smac/diablo, and only a few apoptotic beta cells were found in SHP KO pancreas through inactivation of caspase-3, compared to those of WT. These data demonstrate that SHP deficiency ameliorates hyperglycemia and preserves islet function by inhibiting apoptosis of pancreatic beta cells and up-regulating of their enriched transcriptional factors.

ISSN 

1357-2725

Link 

http://dx.doi.org/10.1016/j.biocel.2013.05.004

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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