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- Lectures
- Institute of Biomedical Sciences
- Location
B1B Lecture Room, IBMS
- Speaker Name
Dr. Kenju Shimomura (Fukushima Medical Univ.)
- State
Definitive
- Url
2024-07-23 13:30 - 14:30
ATP-sensitive K+ (KATP) channel is a key regulator of insulin secretion in pancreatic beta-cell. Recent revelation of high-resolution structures of KATP channel indicate the detail possible mechanisms for the regulation of KATP channel activity.
The gain of function mutations in KATP channel consisting Kir6.2 and SUR1 subunits cause neonatal diabetes. The most severe phenotype of neonatal diabetes is known as DEND syndrome, which presents severe neurological symptoms (epilepsy, muscle weakness and developmental disorder) in addition to hyperglycemia.
We have focused on R50P mutation of Kir6.2, which is known to present severe DEND syndrome. The ATP sensitivity is severely impaired in KATP channel with R50P mutation in Kir6.2. In order to investigate the underlying mechanisms for impaired ATP sensitivity, we have performed molecular dynamics simulation with R50P mutation and investigated the stability of ATP binding to Kir6.2 with R50P mutation.
Also, we are focusing on the study of oxytocin one of the rare hormone/neuropeptide that is expected to cure autism symptom that is also observed in DEND syndrome patients.
