Chapter 4. Postprandial Anti-hyperglycemic Effect of
5.2. Future directions
Ongoing and future work toward addressing the three objectives are outlined below.
• Reaction kinetics study
Inhibitory kinetic assays will be performed to identify the mode of inhibition over α-glucosidase and executed by graphical means of employing primary (Lineweaver-Burk) and secondary plots.
• Molecular docking
To understand the binding interaction with α-glucosidase the molecular
docking will be conducted against the homology model of α-glucosidase.
• Molecular dynamic simulation
MD simulations will be performed for α-glucosidase-vitamin B6 complex.
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Figure 16. Pyridoxine binding to human lysosomal alpha-glucosidase. The catalytic nucleophile and acid/base can be assigned to D518 and D616, respectively. The substrate is stabilized by hydrogen bonds to the side-chains of D404 and W481.
Figure 17. Pyridoxine binding to human lysosomal alpha-glucosidase. Model of Pyridoxine bound to human lysosomal alpha-glucosidase in surface representation.
국문 초록
일반적인 포도당 대사질환인 제 2 형 당뇨병은 인슐린에 대한
체내의 저항성 증가 또는 maltose, sucrose 와 같은 이당류가 함유된
고칼로리 식품의 섭취 등이 주요 원인이다. 제2 형 당뇨병은 성인 당뇨병
환자의 대부분을 차지하는데 2030 년까지 세계적으로 그 수가
3 억 6 천 6 백만명에 이를 것으로 예상된다.
제 2 형 당뇨병을 개선하는데 있어 식후 혈당 조절이 매우
중요한데 식후 높은 혈당 수치는 제 2 형 당뇨병 환자에게 전형적으로
나타나는 증상으로 이는 췌장 α-amylase 와 소장에서의 탄수화물 소화,
흡수에 따른 혈당 상승이 그 원인이다. 식후 혈당 수치를 낮추는 방법은
소장에서 작용하는 glucosidase 의 억제를 통해 가능하기 때문에
α-glucosidase 억제 의약품인 아카보스(Acarbose® , Bayer AG),
보글리보스(Voglibose® , Takeda) 및 미글리톨(Miglitol® , Bayer AG) 등이
일반적으로 제 2 형 당뇨병환자에게 단독 혹은 인슐린 관련 치료제와
비타민 B6(피리독신)는 고령자의 정상 인지 기능을 유지하고
관상동맥 심장질환(CHD) 발병률을 낮추는데 사용되어 왔다. 비타민
B6 의 투여가 당뇨 합병증과 신경퇴행성 질환 발생률을 감소시키며,
또한 제 1 형과 제 2 형 당뇨병의 발병 환자에서 체내 비타민 B6 의 감소를
확인한 바가 보고되었다. 그러나 비타민 B6 와 그 유도체의 식후 혈당
감소 효과 및 작용기전을 제안하는 연구는 거의 없었다. 따라서 본
논문에서는 비타민 B6 와 그 유도체의 식후 혈당 효능과 그 작용기전에
대한 연구를 수행하였으며, 이를 통해 제 2 형 당뇨병의 관리와 예방에
기여하고자 하였다.
먼저 α-glucosidase, sucrase, maltase, glucoamylase 와 같은 다양한
소화 효소에 대한 피리독신, 피리독살, 피리독사민의 억제 활성을
조사하였다. 이당류의 흡수에 관여하는 효소를 억제함으로써 탄수화물
위주의 식이로 인한 식후 고혈당증을 개선할 수 있는데, IC50 실험
위주의 식이로 인한 식후 고혈당증을 개선할 수 있는데, IC50 실험