Abstract:
:Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon hepatitis C virus (HCV) infection. HCV-induced HDAC9 upregulation enhances gluconeogenesis by promoting the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, indicating a major role for HDAC9 in the development of HCV-associated exaggerated gluconeogenic responses. Moreover, HDAC9 expression levels and gluconeogenic activities were elevated in livers from HCV-infected patients and persistent HCV-infected mice, emphasizing the clinical relevance of these results. Our results suggest HDAC9 is involved in glucose metabolism, HCV-induced abnormal glucose homeostasis, and type 2 diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Chen J,Wang N,Dong M,Guo M,Zhao Y,Zhuo Z,Zhang C,Chi X,Pan Y,Jiang J,Tang H,Niu J,Yang D,Li Z,Han X,Wang Q,Chen Xdoi
10.2337/db15-0197subject
Has Abstractpub_date
2015-12-01 00:00:00pages
4088-98issue
12eissn
0012-1797issn
1939-327Xpii
db15-0197journal_volume
64pub_type
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