Biochemistry of AMPK: Mechanisms of Action and Importance in the Treatment of Diabetes

Abstract

As an energy sensor, 5′-adenosine monophosphate (AMP) - activated protein kinase (AMPK) coordinates metabolic pathways to maximize cell energy requirements. AMPK, a serine / threonine protein complex, consists of three main subunits. Molecular regulation of AMPK is achieved by phosphorylation of these three main subunits. AMPK is activated at low energy levels (AMP / ADP: ATP). When AMPK is activated in metabolism, anabolic reactions are inhibited and catabolic reactions are activated. When AMPK is activated, protein, fatty acids, glycogen and cholesterol synthesis are inhibited while oxidation of fatty acids, translocation of the GLUT4 protein, and the destruction of damaged cells (autophagy) are activated. Activation of AMPK is also mediated by LKB1 (serine – threonine kinase liver kinase B1) and CaMKKβ (Ca2+ / calmodulin-dependent protein kinase β) kinases. Some drugs such as metformin also mediate activation of AMPK in the treatment of diabetes. In addition to pharmaceutical drugs, a large number of naturally occurring phytochemical compounds, especially some polyphenols, have been shown to activate AMPK. These polyphenols have been reported to both activate AMPK and reduce the complications of Type 2 diabetes. Among these, the most known and active polyphenols are resveratrol, quercetin and kurmumin. In addition, vitamin D and vitamin K1 activate AMPK and increase the translocation of GLUT4. As seen, increasing the activation of AMPK has been shown to be important in the treatment of many diseases, especially diabetes. In addition to exercise, it appears to have an important role of functional nutrients and vitamins in increasing the activation of AMPK.

Keywords

• AMPK
• GLUT4
• Diabetes
• Insulin
• Phenolic compounds
• Vitamin

AMPK'nin Biyokimyası: Etki Mekanizmaları ve Diyabetin Tedavisindeki Önemi

Abstract

Bir enerji sensörü olarak, 5′-adenosine monophosphate (AMP)- ile aktive edilmiş protein kinaz (AMPK), metabolik yolları koordine ederek hücre enerji gereksinimini maksimum seviyede düzenler. Bir serin/ treonin protein kompleksi olan AMPK, üç ana alt birimden oluşur. AMPK’nın moleküler regülasyonu bu üç ana alt birimin fosforilasyonu ile olmaktadır. AMPK, düşük enerji seviyelerinde (AMP/ADP:ATP) aktive olmaktadır. Metabolizmada AMPK aktive olduğunda anabolik reaksiyonlar inhibe edilirken katabolik reaksiyonlar aktive edilmektedir. AMPK aktive olduğunda protein, yağ asitleri, glikojen ve kolesterol sentezi inhibe edilirken yağ asitlerinin oksidasyonu, kan glikoz seviyesini düzenlemede insülinden bağımsız bir şekilde GLUT4 proteininin translokasyonu ve hasarlı hücrelerin yok edilmesi (otofaji) işlemini aktive edilir. AMPK’nın aktivasyonu LKB1 (serine–threonine kinase liver kinase B1) ve CaMKKβ (Ca2+/calmodulin-dependent protein kinase β) kinazları tarafından da olmaktadır. Diyabetin tedavisinde AMPK’nın aktivasyonu metformin gibi bazı ilaçlar tarafından da olmaktadır. Farmasötik ilaçlara ek olarak, çok sayıda doğal olarak bulunan fitokimyasal bileşikler özellikle bazı polifenoller AMPK'yı aktive ettiği gösterilmiştir. Bu polifenollerün hem AMPK'yi aktive ettiği hem de Tip 2 diyabetin komplikasyonlarını azalttığı da görülmüştür. Bunlar arasında en fazla bilinen polifenoller resveratrol, kuersetin ve kurmumin’dir. Bunlara ek olarak D vitamini ve K1 vitamininin de AMPK’yı aktive ettiği ve GLUT4’ın traslokasyonunu arttırdığı da görülmüştür. Görüldüğü gibi AMPK’nın aktivasyonunun arttırılması diyabet başta olmak üzere birçok hastalığın tedavisinde önemli olduğu görülmüştür. AMPK’nın aktivasyonununun artırılmasında egzersizin yanında fonksiyonel besinlerin ve vitaminlerinde önemli bir yeri olduğu görülmektedir.

Keywords

• AMPK
• GLUT4
• Diyabet
• İnsülin
• Fenolik bileşikler
• vitamin

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