PMID- 23026370
OWN - NLM
STAT- MEDLINE
DCOM- 20130417
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 696
IP  - 1-3
DP  - 2012 Dec 5
TI  - A compound (DW1182v) protecting high glucose/palmitate-induced glucolipotoxicity 
      to INS-1 beta cells preserves islet integrity and improves hyperglycemia in obese 
      db/db mouse.
PG  - 187-93
LID - S0014-2999(12)00797-2 [pii]
LID - 10.1016/j.ejphar.2012.09.023 [doi]
AB  - Loss of beta cells is a pathogenic cause for the development of type 2 diabetes. 
      High glucose/free fatty acid (HG/FFA)-induced glucolipotoxicity was thought to 
      play a role in the beta cell loss. Thus, application of small molecules capable 
      of preventing HG/FFA-induced glucolipotoxicty to beta cells could be an avenue 
      for a therapeutic intervention for the development of type 2 diabetes. We 
      screened a representative library supplied from Korean Chemical Bank for 
      prevention of high glucose/palmitate (HG/PA)-induced viability reduction of INS-1 
      beta cells and were able to identify a new small molecule (DW1182v) with a 
      function to protect HG/PA-induced glucolipotoxicity. The protective effect was 
      specific to HG/PA-induced beta cell death since DW1182v did not protect 
      streptozotocin- or cytokine-induced INS-1 cell death. The protective effect by 
      DW1182v was likely due to the reduction of death-promoting endoplasmic reticulum 
      (ER) stress responses such as phospho-C-Jun N-terminal kinase (JNK) and C/EBP 
      homologous protein (CHOP). Treatment of obese diabetic db/db mice with DW1182v 
      preserved islet integrity and thus increased insulin secretion and lowered blood 
      glucose after glucose infusion. These results suggest that a small molecule 
      protecting HG/PA-induced glucolipotoxicity to beta cells can be a new therapeutic 
      candidate to prevent the development of type 2 diabetes.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Lee, Soo-Jin
AU  - Lee SJ
AD  - Institute for Medical Sciences, Ajou University School of Medicine, Suwon 
      442-749, Republic of Korea.
FAU - Choi, Sung-E
AU  - Choi SE
FAU - Hwang, Yun Cheong
AU  - Hwang YC
FAU - Jung, Ik-Rak
AU  - Jung IR
FAU - Yi, Sang-A
AU  - Yi SA
FAU - Jung, Jong Gab
AU  - Jung JG
FAU - Ku, Jin-Mo
AU  - Ku JM
FAU - Jeoung, Kwiwan
AU  - Jeoung K
FAU - Han, Seung Jin
AU  - Han SJ
FAU - Kim, Hae Jin
AU  - Kim HJ
FAU - Kim, Dae Jung
AU  - Kim DJ
FAU - Lee, Kwan-Woo
AU  - Lee KW
FAU - Kang, Yup
AU  - Kang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120928
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (4-(1H-indazol-6-ylamino)-N-isopropyl-2-(methylthio)pyrimidine-5-carboxamide)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Indazoles)
RN  - 0 (Insulin)
RN  - 0 (Palmitates)
RN  - 0 (Pyrimidines)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Endoplasmic Reticulum Stress/drug effects
MH  - Glucose/pharmacology
MH  - Glucose Tolerance Test
MH  - Hyperglycemia/blood/drug therapy/pathology
MH  - Hypoglycemic Agents/*pharmacology/therapeutic use
MH  - Indazoles/*pharmacology/therapeutic use
MH  - Insulin/blood
MH  - Insulin-Secreting Cells/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Obese
MH  - Obesity/blood/drug therapy/pathology
MH  - Palmitates/pharmacology
MH  - Pyrimidines/*pharmacology/therapeutic use
EDAT- 2012/10/03 06:00
MHDA- 2013/04/18 06:00
CRDT- 2012/10/03 06:00
PHST- 2012/04/12 00:00 [received]
PHST- 2012/07/30 00:00 [revised]
PHST- 2012/09/06 00:00 [accepted]
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/04/18 06:00 [medline]
AID - S0014-2999(12)00797-2 [pii]
AID - 10.1016/j.ejphar.2012.09.023 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2012 Dec 5;696(1-3):187-93. doi: 10.1016/j.ejphar.2012.09.023. 
      Epub 2012 Sep 28.