214 638

Cited 0 times in

β-Cell-protective effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid as a glutamate dehydrogenase activator in db/db mice

Authors
 송제은  ;  오동현  ;  김민형  ;  김용찬  ;  안진영  ;  정수진  ;  구남수  ;  김혜원  ;  김선빈  ;  한상훈  ;  최준용  ;  김창오  ;  송영구  ;  김준명 
Citation
 JOURNAL OF ENDOCRINOLOGY, Vol.212(3) : 307-315, 2012 
Journal Title
JOURNAL OF ENDOCRINOLOGY
ISSN
 0022-0795 
Issue Date
2012
MeSH
Amino Acids, Cyclic/pharmacology* ; Animals ; Apoptosis/drug effects ; Blood Glucose/analysis ; Cell Line, Tumor ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/physiopathology* ; Drug Synergism ; Enzyme Activation/drug effects ; Gene Expression/drug effects ; Glucose/pharmacology ; Glutamate Dehydrogenase/physiology* ; Insulin/blood ; Insulin/genetics ; Insulin/secretion ; Insulin-Secreting Cells/drug effects* ; Insulin-Secreting Cells/physiology* ; Insulinoma ; Mice ; Pancreatic Neoplasms ; Rats
Keywords
Amino Acids, Cyclic/pharmacology* ; Animals ; Apoptosis/drug effects ; Blood Glucose/analysis ; Cell Line, Tumor ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/physiopathology* ; Drug Synergism ; Enzyme Activation/drug effects ; Gene Expression/drug effects ; Glucose/pharmacology ; Glutamate Dehydrogenase/physiology* ; Insulin/blood ; Insulin/genetics ; Insulin/secretion ; Insulin-Secreting Cells/drug effects* ; Insulin-Secreting Cells/physiology* ; Insulinoma ; Mice ; Pancreatic Neoplasms ; Rats
Abstract
2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is an activator of glutamate dehydrogenase (GDH), which is a mitochondrial enzyme with an important role in insulin secretion. We investigated the effect of BCH on the high-glucose (HG)-induced reduction in glucose-stimulated insulin secretion (GSIS), the HG/palmitate (PA)-induced reduction in insulin gene expression, and HG/PA-induced β-cell death. We also studied whether long-term treatment with BCH lowers blood glucose and improves β-cell integrity in db/db mice. We evaluated GSIS, insulin gene expression, and DNA fragmentation in INS-1 cells exposed to HG or HG/PA in the presence or absence of BCH. An in vivo study was performed in which 7-week-old diabetic db/db mice were treated with BCH (0.7  g/kg, n = 10) and placebo (n = 10) every other day for 6 weeks. After treatment, an intraperitoneal glucose tolerance test and immunohistological examinations were performed. Treatment with BCH blocked HG-induced GSIS inhibition and the HG/PA-induced reduction in insulin gene expression in INS-1 cells. In addition, BCH significantly reduced HG/PA-induced INS-1 cell death and phospho-JNK level. BCH treatment improved glucose tolerance and insulin secretion in db/db mice. BCH treatment also increased the ratio of insulin-positive β-cells to total islet area (P < 0.05) and reduced the percentage of β-cells expressing cleaved caspase 3 (P < 0.05). In conclusion, the GDH activator BCH improved glycemic control in db/db mice. This anti-diabetic effect may be associated with improved insulin secretion, preserved islet architecture, and reduced β-cell apoptosis.
Files in This Item:
T201203435.pdf Download
DOI
22131441
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Hyun Chul(이현철)
Han, Seung Jin(한승진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90778
사서에게 알리기
  feedback

qrcode

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

Browse

Links