PMID- 30066289
OWN - NLM
STAT- MEDLINE
DCOM- 20190221
LR  - 20190221
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 41
IP  - 6
DP  - 2018 Dec
TI  - Inhibition of NF-kappaB Reduces Renal Inflammation and Expression of PEPCK in Type 2 
      Diabetic Mice.
PG  - 2018-2029
LID - 10.1007/s10753-018-0845-0 [doi]
AB  - Renal gluconeogenesis is markedly promoted in patients with type 2 diabetes 
      mellitus (T2DM); however, the underlying mechanism remains largely unknown. Renal 
      gluconeogenesis is found to be negatively regulated by insulin. T2DM is 
      characterized by chronic and subacute inflammation; however, inflammation has 
      been well recognized to induce insulin resistance. Therefore, this study aimed to 
      investigate whether the enhanced renal gluconeogenesis in T2DM was partially due 
      to the renal inflammation-mediated insulin resistance. If so, whether 
      inflammation inhibitor could partially reverse such change. Diabetic db/db mice 
      and db/m mice were used in our study. Typically, diabetic db/db mice were 
      intraperitoneally treated with 1 mg/kg NF-kappaB inhibitor parthenolide (PTN) or 
      saline as control every other day. Twelve weeks after treatment, animal samples 
      were collected for measurements. Our results suggested that the expression levels 
      of the inflammatory factors and the gluconeogenic rate-limiting enzyme 
      phosphoenolpyruvate carboxykinase (PEPCK) were up-regulated in renal cortex of 
      both db/db mice and T2DM patients. Moreover, reduced insulin signaling, as well 
      as up-regulated expression of downstream genes FOXO1 and PGC-1a, could be 
      detected in renal cortex of db/db mice compared with that of db/m mice. 
      Consistent with our hypothesis, PTN treatment could alleviate renal inflammation 
      and insulin resistance in db/db mice. Moreover, it could also down-regulate the 
      renal expression of PEPCK, indicating that inflammation could be one of the 
      triggers of insulin resistance and the enhanced renal gluconeogenesis in db/db 
      mice. This study can shed light on the role of inflammation in the enhanced renal 
      gluconeogenesis in T2DM, which may yield a novel target for hyperglycemia.
FAU - Liu, Qianling
AU  - Liu Q
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Zhang, Liangyan
AU  - Zhang L
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Hao, Qiufa
AU  - Hao Q
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Qiu, Wei
AU  - Qiu W
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Wen, Yubing
AU  - Wen Y
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Wang, Haiyun
AU  - Wang H
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.
FAU - Li, Xuemei
AU  - Li X
AD  - Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy 
      of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China. 
      lixmpumch@126.com.
LA  - eng
GR  - 7122143/Natural Science Foundation of Beijing Municipality/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (NF-kappa B)
RN  - 0 (Sesquiterpenes)
RN  - 2RDB26I5ZB (parthenolide)
RN  - EC 4.1.1.32 (Phosphoenolpyruvate Carboxykinase (GTP))
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Diabetes Mellitus, Experimental
MH  - Diabetes Mellitus, Type 2/*pathology
MH  - Gluconeogenesis
MH  - Inflammation/complications/drug therapy/*prevention & control
MH  - Insulin Resistance
MH  - Kidney/metabolism/pathology
MH  - Mice
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Phosphoenolpyruvate Carboxykinase (GTP)/*metabolism
MH  - Sesquiterpenes/pharmacology
OTO - NOTNLM
OT  - inflammation
OT  - insulin resistance
OT  - renal gluconeogenesis
OT  - type 2 diabetes mellitus
EDAT- 2018/08/02 06:00
MHDA- 2019/02/23 06:00
CRDT- 2018/08/02 06:00
PHST- 2018/08/02 06:00 [pubmed]
PHST- 2019/02/23 06:00 [medline]
PHST- 2018/08/02 06:00 [entrez]
AID - 10.1007/s10753-018-0845-0 [pii]
AID - 10.1007/s10753-018-0845-0 [doi]
PST - ppublish
SO  - Inflammation. 2018 Dec;41(6):2018-2029. doi: 10.1007/s10753-018-0845-0.