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Your search keyword '"Yaohui Nie"' showing total 2 results
Start Over Author "Yaohui Nie" Publisher american society for clinical investigation
2 results on '"Yaohui Nie"'

1. MAPK phosphatase–3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice

Author

Phillip Hwang, Xueming Huang, Yaohui Nie, Guozhi Xiao, Jing Du, Shengyong Yang, Yajun Feng, Zhidan Wu, Haiyan Xu, Ping Jiao, and Bin Feng

Subjects
MAPK/ERK pathway, Male, medicine.medical_specialty, Mice, Obese, FOXO1, Biology, Carbohydrate metabolism, Transfection, Dephosphorylation, Mice, Insulin resistance, Dual Specificity Phosphatase 6, Internal medicine, medicine, Animals, Insulin, RNA, Small Interfering, Transcription factor, Forkhead Box Protein O1, Body Weight, Gluconeogenesis, nutritional and metabolic diseases, Forkhead Transcription Factors, General Medicine, Fasting, medicine.disease, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mice, Inbred C57BL, Endocrinology, Glucose, Diabetes Mellitus, Type 2, Liver, MAPK phosphatase, Trans-Activators, Research Article, Transcription Factors
Abstract

Insulin resistance results in dysregulated hepatic gluconeogenesis that contributes to obesity-related hyperglycemia and progression of type 2 diabetes mellitus (T2DM). Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. Here, we have shown that expression of MKP-3 is markedly increased in the liver of diet-induced obese mice. Consistent with this, adenovirus-mediated MKP-3 overexpression in lean mice promoted gluconeogenesis and increased fasting blood glucose levels. Conversely, shRNA knockdown of MKP-3 in both lean and obese mice resulted in decreased fasting blood glucose levels. In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. These data indicate that MKP-3 is an important regulator of hepatic gluconeogenesis in vivo and suggest that inhibition of MKP-3 activity may provide new therapies for T2DM.

Published
2010

2. MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice.

Author

Zhidan Wu, Ping Jiao, Xueming Huang, Bin Feng, Yajun Feng, Shengyong Yang, Phillip Hwang, Jing Du, Yaohui Nie, Guozhi Xiao, Haiyan Xu, Wu, Zhidan, Jiao, Ping, Huang, Xueming, Feng, Bin, Feng, Yajun, Yang, Shengyong, Hwang, Phillip, Du, Jing, and Nie, Yaohui

Subjects
*MITOGEN-activated protein kinases, *GLUCONEOGENESIS, *INSULIN resistance, *GENETIC regulation, *HYPERGLYCEMIA treatment, *TREATMENT of diabetes, *GENE expression, *LABORATORY mice, *PROTEIN metabolism, *RNA metabolism, *GLUCOSE metabolism, *ANIMAL experimentation, *BODY weight, *COMPARATIVE studies, *FASTING, *GENETIC techniques, *INSULIN, *LIVER, *RESEARCH methodology, *MEDICAL cooperation, *METABOLISM, *MICE, *TYPE 2 diabetes, *PHOSPHATASES, *PROTEINS, *RESEARCH, *RNA, *TRANSCRIPTION factors, *EVALUATION research
Abstract

Insulin resistance results in dysregulated hepatic gluconeogenesis that contributes to obesity-related hyperglycemia and progression of type 2 diabetes mellitus (T2DM). Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. Here, we have shown that expression of MKP-3 is markedly increased in the liver of diet-induced obese mice. Consistent with this, adenovirus-mediated MKP-3 overexpression in lean mice promoted gluconeogenesis and increased fasting blood glucose levels. Conversely, shRNA knockdown of MKP-3 in both lean and obese mice resulted in decreased fasting blood glucose levels. In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. These data indicate that MKP-3 is an important regulator of hepatic gluconeogenesis in vivo and suggest that inhibition of MKP-3 activity may provide new therapies for T2DM. [ABSTRACT FROM AUTHOR]

Published
2010
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