138 509

Cited 4 times in

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

Lee, SJ; Choi, SE; Hwang, YC; Jung, IR; Yi, SA; Jung, JG; Ku, JM; Jeoung, K; Han, SJ; Kim, HJ; Kim, DJ; Lee, KW; Kang, Y
European journal of pharmacology, 696(1-3):187-193, 2012
Journal Title
European journal of pharmacology
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.
MeSH terms
AnimalsBlood Glucose/analysisCell LineCell Survival/drug effectsEndoplasmic Reticulum Stress/drug effectsGlucose/pharmacologyGlucose Tolerance TestHyperglycemia/blood/drug therapy/pathologyHypoglycemic Agents/*pharmacology/therapeutic useIndazoles/*pharmacology/therapeutic useInsulin/bloodInsulin-Secreting Cells/*drug effectsMaleMiceMice, ObeseObesity/blood/drug therapy/pathologyPalmitates/pharmacologyPyrimidines/*pharmacology/therapeutic use
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
한, 승진김, 혜진김, 대중이, 관우강, 엽
Full Text Link
Files in This Item:
There are no files associated with this item.
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.