Aşırı beslenmeye bağlı oluşan insülin direncinin biyokimyasal gelişimi ve AMP-ile aktive edilmiş protein kinaz (AMPK)’ın fonksiyonu

Year 2020, Issue: 20, 67 - 76, 31.12.2020

Mustafa Yaman , Cemalettin Kismiroğlu , Halime Uğur , İsmail Belli , Bahtiyar Özgür

https://doi.org/10.31590/ejosat.746132

Cited By: 1

Abstract

Aşırı beslenme ve obezitenin, insülin direnci, diyabet, hipertansiyon, kardiyovasküler hastalıklar ve kanser gibi birçok kronik hastalığa neden olduğu bilinmektedir. İnsülin direnci, glikozun kas ve diğer dokulara taşınmasında hücrelerin insülininin etkisine yanıt verme yeteneğinin azalması olarak tanımlanır. Obezitenin gelişmesiyle birlikte yağ dokusundan salınan esterlenmemiş yağ asitleri, gliserol ve proinflamatuar sitokinler insülin direncine neden olur. Özellikle MCP-1 ve TNF-α gibi sitokin ve kemokinler adipositlerde trigliseridlerin hidrolizine neden olur. Ortaya çıkan serbest yağ asitleri dolaşım yoluyla kas, karaciğer ve beta hücrelerine taşınır ve DAG, TAG ve seramid olarak depolanır. Bu yağ asitleri türevlerinin birikimi hem IRS’yi bloke ederek insülin direncine, hemde hücre içi enerji sensörü olan AMPK’nin aktivasyonunun azalmasına neden olur. AMPK’nin aktivasyonunun azalması sonucu glukoz taşıyıcı proteininin translokasyonu azalır ve insülin direnci gelişir. Bunun yanında, AMPK’nin aktivasyonunun azalması dokularda lipit birikimine, hücresel işlev bozukluklarına ve birçok kronik hastalığın gelişmesine neden olur. Egzersizin yanında metformin, AICAR ve TZDs gibi bazı farmasötik ilaçların hem lipit birikimini azalttığı hem de AMPK’nin aktivasyonunu artırarak insülin direncini engellediği bildirilmiştir

Keywords

İnsülin direnci, Obezite, AMPK, Sitokinler

Biochemical development of insulin resistance due to excess nutrition and the function of AMP-activated protein kinase (AMPK)

Abstract

Overnutrition and obesity are known to cause many chronic diseases such as insulin resistance, diabetes, and cancer. Insulin resistance is defined as a decrease in the ability of cells to respond to the effect of insulin in the transport of glucose to muscle and other tissues. With the development of obesity, nonesterified fatty acids, glycerol, hormones, pro-inflammatory cytokines released from adipose tissue are known to play a role in the development of insulin resistance. Especially cytokines and chemokines such as MCP-1 and TNFα cause hydrolysis of triglycerides in adipocytes, causing high levels of free fatty acids in circulation. These free fatty acids are then stored by the muscle and liver and beta cells again as DAG, TAG, and ceramide, blocking the IRS receptor causing its resistance. In addition, as a result of excessive fat nutrition, the accumulation of toxic lipid derivatives causes the inactivation of the intracellular energy sensor AMPK. Depending on the inactivation of AMPK, the glucose carrier protein (GLUT4) translocation decreases, and insulin resistance improves. Also, reduced activation of AMPK causes lipid accumulation in tissues, cellular dysfunctions, and, consequently, many chronic diseases. In addition to exercise, it is seen that some pharmaceutical drugs such as metformin, AICAR, and TZDs both reduce lipid accumulation and increase the activation of AMPK and prevent insulin resistance

Keywords

Insulin resistance, Obesity, AMPK

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