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AMPK'nin Biyokimyası: Etki Mekanizmaları ve Diyabetin Tedavisindeki Önemi

Yıl 2020, Sayı: 18, 162 - 170, 15.04.2020
https://doi.org/10.31590/ejosat.676335

Öz

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.

Destekleyen Kurum

İstanbul Sabahttin Zaim Üniveristesi

Kaynakça

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  • Anand, P., Murali, K. Y., Tandon, V., Murthy, P. S., & Chandra, R. (2010). Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chemico-biological interactions, 186(1), 72-81.
  • Ao, Z., Quezada-Calvillo, R., Sim, L., Nichols, B. L., Rose, D. R., Sterchi, E. E., & Hamaker, B. R. (2007). Evidence of native starch degradation with human small intestinal maltase‐glucoamylase (recombinant). FEBS letters, 581(13), 2381-2388.
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  • Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α‐amylase and starch digestion: An interesting marriage. Starch‐Stärke, 63(7), 395-405.
  • Calamaras, T. D., Lee, C., Lan, F., Ido, Y., Siwik, D. A., & Colucci, W. S. (2012). Post-translational modification of serine/threonine kinase LKB1 via adduction of the reactive lipid species 4-hydroxy-trans-2-nonenal (HNE) at lysine residue 97 directly inhibits kinase activity. Journal of Biological Chemistry, 287(50), 42400-42406.
  • Chen, T. C., & Hsieh, S. S. (2000). The effects of repeated maximal voluntary isokinetic eccentric exercise on recovery from muscle damage. Research quarterly for exercise and sport, 71(3), 260-266.
  • Choi, S. L., Kim, S. J., Lee, K. T., Kim, J., Mu, J., Birnbaum, M. J., ... & Ha, J. (2001). The regulation of AMP-activated protein kinase by H2O2. Biochemical and biophysical research communications, 287(1), 92-97.
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  • Dihingia, A., Ozah, D., Ghosh, S., Sarkar, A., Baruah, P. K., Kalita, J., ... & Manna, P. (2018). Vitamin K1 inversely correlates with glycemia and insulin resistance in patients with type 2 diabetes (T2D) and positively regulates SIRT1/AMPK pathway of glucose metabolism in liver of T2D mice and hepatocytes cultured in high glucose. The Journal of nutritional biochemistry, 52, 103-114
  • Doran, E., & Halestrap, A. P. (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochemical Journal, 348(3), 607-614.
  • Du, M., Shen, Q. W., Zhu, M. J., & Ford, S. P. (2007). Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase. Journal of animal science, 85(4), 919-927.
  • Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014). Metformin: from mechanisms of action to therapies. Cell metabolism, 20(6), 953-966.
  • Frøsig, C., Pehmøller, C., Birk, J. B., Richter, E. A., & Wojtaszewski, J. F. (2010). Exercise‐induced TBC1D1 Ser237 phosphorylation and 14‐3‐3 protein binding capacity in human skeletal muscle. The Journal of physiology, 588(22), 4539-4548.
  • Fryer, L. G., Parbu-Patel, A., & Carling, D. (2002). The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. Journal of Biological Chemistry, 277(28), 25226-25232.
  • Fujii, N., Hayashi, T., Hirshman, M. F., Smith, J. T., Habinowski, S. A., Kaijser, L., ... & Thorell, A. (2000). Exercise induces isoform-specific increase in 5′ AMP-activated protein kinase activity in human skeletal muscle. Biochemical and biophysical research communications, 273(3), 1150-1155.
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  • Gledhill, J. R., Montgomery, M. G., Leslie, A. G., & Walker, J. E. (2007). Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proceedings of the National Academy of Sciences, 104(34), 13632-13637.
  • Habegger, K. M., Hoffman, N. J., Ridenour, C. M., Brozinick, J. T., & Elmendorf, J. S. (2012). AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology, 153(5), 2130-2141.
  • Habets, D. D., Coumans, W. A., El Hasnaoui, M., Zarrinpashneh, E., Bertrand, L., Viollet, B., ... & Glatz, J. F. (2009). Crucial role for LKB1 to AMPKα2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1791(3), 212-219.
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Biochemistry of AMPK: Mechanisms of Action and Importance in the Treatment of Diabetes

Yıl 2020, Sayı: 18, 162 - 170, 15.04.2020
https://doi.org/10.31590/ejosat.676335

Öz

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.

Kaynakça

  • Ahn, J., Lee, H., Kim, S., Park, J., & Ha, T. (2008). The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochemical and biophysical research communications, 373(4), 545-549.
  • Anand, P., Murali, K. Y., Tandon, V., Murthy, P. S., & Chandra, R. (2010). Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chemico-biological interactions, 186(1), 72-81.
  • Ao, Z., Quezada-Calvillo, R., Sim, L., Nichols, B. L., Rose, D. R., Sterchi, E. E., & Hamaker, B. R. (2007). Evidence of native starch degradation with human small intestinal maltase‐glucoamylase (recombinant). FEBS letters, 581(13), 2381-2388.
  • Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Pistell, P. J. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444(7117), 337.
  • Brunmair, B., Staniek, K., Gras, F., Scharf, N., Althaym, A., Clara, R., ... & Fürnsinn, C. (2004). Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?. Diabetes, 53(4), 1052-1059.
  • Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α‐amylase and starch digestion: An interesting marriage. Starch‐Stärke, 63(7), 395-405.
  • Calamaras, T. D., Lee, C., Lan, F., Ido, Y., Siwik, D. A., & Colucci, W. S. (2012). Post-translational modification of serine/threonine kinase LKB1 via adduction of the reactive lipid species 4-hydroxy-trans-2-nonenal (HNE) at lysine residue 97 directly inhibits kinase activity. Journal of Biological Chemistry, 287(50), 42400-42406.
  • Chen, T. C., & Hsieh, S. S. (2000). The effects of repeated maximal voluntary isokinetic eccentric exercise on recovery from muscle damage. Research quarterly for exercise and sport, 71(3), 260-266.
  • Choi, S. L., Kim, S. J., Lee, K. T., Kim, J., Mu, J., Birnbaum, M. J., ... & Ha, J. (2001). The regulation of AMP-activated protein kinase by H2O2. Biochemical and biophysical research communications, 287(1), 92-97.
  • Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., Phisalaphong, C., & Jirawatnotai, S. (2012). Curcumin extract for prevention of type 2 diabetes. Diabetes care, 35(11), 2121-2127.
  • Coughlan, K. A., Valentine, R. J., Ruderman, N. B., & Saha, A. K. (2013). Nutrient excess in AMPK downregulation and insulin resistance. Journal of endocrinology, diabetes & obesity, 1(1), 1008.
  • Dihingia, A., Ozah, D., Ghosh, S., Sarkar, A., Baruah, P. K., Kalita, J., ... & Manna, P. (2018). Vitamin K1 inversely correlates with glycemia and insulin resistance in patients with type 2 diabetes (T2D) and positively regulates SIRT1/AMPK pathway of glucose metabolism in liver of T2D mice and hepatocytes cultured in high glucose. The Journal of nutritional biochemistry, 52, 103-114
  • Doran, E., & Halestrap, A. P. (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochemical Journal, 348(3), 607-614.
  • Du, M., Shen, Q. W., Zhu, M. J., & Ford, S. P. (2007). Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase. Journal of animal science, 85(4), 919-927.
  • Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014). Metformin: from mechanisms of action to therapies. Cell metabolism, 20(6), 953-966.
  • Frøsig, C., Pehmøller, C., Birk, J. B., Richter, E. A., & Wojtaszewski, J. F. (2010). Exercise‐induced TBC1D1 Ser237 phosphorylation and 14‐3‐3 protein binding capacity in human skeletal muscle. The Journal of physiology, 588(22), 4539-4548.
  • Fryer, L. G., Parbu-Patel, A., & Carling, D. (2002). The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. Journal of Biological Chemistry, 277(28), 25226-25232.
  • Fujii, N., Hayashi, T., Hirshman, M. F., Smith, J. T., Habinowski, S. A., Kaijser, L., ... & Thorell, A. (2000). Exercise induces isoform-specific increase in 5′ AMP-activated protein kinase activity in human skeletal muscle. Biochemical and biophysical research communications, 273(3), 1150-1155.
  • Fulco, M., & Sartorelli, V. (2008). Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell cycle, 7(23), 3669-3679.
  • Gledhill, J. R., Montgomery, M. G., Leslie, A. G., & Walker, J. E. (2007). Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proceedings of the National Academy of Sciences, 104(34), 13632-13637.
  • Habegger, K. M., Hoffman, N. J., Ridenour, C. M., Brozinick, J. T., & Elmendorf, J. S. (2012). AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology, 153(5), 2130-2141.
  • Habets, D. D., Coumans, W. A., El Hasnaoui, M., Zarrinpashneh, E., Bertrand, L., Viollet, B., ... & Glatz, J. F. (2009). Crucial role for LKB1 to AMPKα2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1791(3), 212-219.
  • Hardie, D. G., & Pan, D. A. (2002). Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase.
  • Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012). AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nature reviews Molecular cell biology, 13(4), 251.
  • Hayashi, T., Hirshman, M. F., Fujii, N. S. A. H., Habinowski, S. A., Witters, L. A., & Goodyear, L. J. (2000). Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes, 49(4), 527-531.
  • Hoppe, S., Bierhoff, H., Cado, I., Weber, A., Tiebe, M., Grummt, I., & Voit, R. (2009). AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proceedings of the National Academy of Sciences, 106(42), 17781-17786.
  • Hunter, R. W., Treebak, J. T., Wojtaszewski, J. F., & Sakamoto, K. (2011). Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes, 60(3), 766-774.
  • Hwang, J. T., Park, I. J., Shin, J. I., Lee, Y. K., Lee, S. K., Baik, H. W., ... & Park, O. J. (2005). Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochemical and biophysical research communications, 338(2), 694-699.
  • Itani, S. I., Saha, A. K., Kurowski, T. G., Coffin, H. R., Tornheim, K., & Ruderman, N. B. (2003). Glucose autoregulates its uptake in skeletal muscle: involvement of AMP-activated protein kinase. Diabetes, 52(7), 1635-1640.
  • Jeon, S. M. (2016). Regulation and function of AMPK in physiology and diseases. Experimental & molecular medicine, 48(7), e245.
  • Kim, J., Yang, G., Kim, Y., Kim, J., & Ha, J. (2016). AMPK activators: mechanisms of action and physiological activities. Experimental & molecular medicine, 48(4), e224.
  • Kim, T., Davis, J., Zhang, A. J., He, X., & Mathews, S. T. (2009). Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells. Biochemical and biophysical research communications, 388(2), 377-382.
  • Koh, H. J., Arnolds, D. E., Fujii, N., Tran, T. T., Rogers, M. J., Jessen, N., ... & Kulkarni, R. N. (2006). Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. Molecular and cellular biology, 26(22), 8217-8227.
  • Kosztelnik, M., Kurucz, A., Papp, D., Jones, E., Sigmond, T., Barna, J., ... & Vellai, T. (2018). Suppression of AMPK/aak-2 by NRF2/SKN-1 down-regulates autophagy during prolonged oxidative stress. The FASEB Journal, 33(2), 2372-2387.
  • LeBrasseur, N. K., Kelly, M., Tsao, T. S., Farmer, S. R., Saha, A. K., Ruderman, N. B., & Tomas, E. (2006). Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. American Journal of Physiology-Endocrinology and Metabolism, 291(1), E175-E181.
  • Lee, Y. S., Kim, W. S., Kim, K. H., Yoon, M. J., Cho, H. J., Shen, Y., ... & Hohnen-Behrens, C. (2006). Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes, 55(8), 2256-2264.
  • Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., ... & Gao, B. (2011). AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell metabolism, 13(4), 376-388.
  • Mann, J., Cummings, J. H., Englyst, H. N., Key, T., Liu, S., Riccardi, G., ... & Vorster, H. H. (2007). FAO/WHO scientific update on carbohydrates in human nutrition: conclusions. European journal of clinical nutrition, 61(S1), S132.
  • Manna, P., Achari, A. E., & Jain, S. K. (2017). Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Archives of biochemistry and biophysics, 615, 22-34.
  • Marsin, A. S., Bertrand, L., Rider, M. H., Deprez, J., Beauloye, C., Vincent, M. F., ... & Hue, L. (2000). Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Current biology, 10(20), 1247-1255.
  • Marsin, A. S., Bouzin, C., Bertrand, L., & Hue, L. (2002). The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. Journal of Biological Chemistry, 277(34), 30778-30783.
  • Mihaylova, M. M., & Shaw, R. J. (2011). The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature cell biology, 13(9), 1016.
  • Minokoshi, Y., Kim, Y. B., Peroni, O. D., Fryer, L. G., Müller, C., Carling, D., & Kahn, B. B. (2002). Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature, 415(6869), 339.
  • Muoio, D. M., Seefeld, K., Witters, L. A., & Coleman, R. A. (1999). AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochemical Journal, 338(3), 783-791.
  • O'neill, H. M. (2013). AMPK and exercise: glucose uptake and insulin sensitivity. Diabetes & metabolism journal, 37(1), 1-21.
  • Ong, K. W., Hsu, A., & Tan, B. K. H. (2012). Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PloS one, 7(3), e32718.
  • Park, C. E., Kim, M. J., Lee, J. H., Min, B. I., Bae, H., Choe, W., ... & Ha, J. (2007). Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase. Experimental & molecular medicine, 39(2), 222.
  • Penumathsa, S. V., Thirunavukkarasu, M., Zhan, L., Maulik, G., Menon, V. P., Bagchi, D., & Maulik, N. (2008). Resveratrol enhances GLUT‐4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. Journal of cellular and molecular medicine, 12(6a), 2350-2361.
  • Roepstorff, C., Thiele, M., Hillig, T., Pilegaard, H., Richter, E. A., Wojtaszewski, J. F., & Kiens, B. (2006). Higher skeletal muscle α2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. The Journal of physiology, 574(1), 125-138.
  • Saha, A. K., Avilucea, P. R., Ye, J. M., Assifi, M. M., Kraegen, E. W., & Ruderman, N. B. (2004). Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochemical and biophysical research communications, 314(2), 580-585.
  • Saha, A. K., Xu, X. J., Balon, T. W., Brandon, A., Kraegen, E. W., & Ruderman, N. B. (2011). Insulin resistance due to nutrient excess: is it a consequence of AMPK downregulation?. Cell Cycle, 10(20), 3447-3451.
  • Saha, A. K., Xu, X. J., Lawson, E., Deoliveira, R., Brandon, A. E., Kraegen, E. W., & Ruderman, N. B. (2010). Downregulation of AMPK accompanies leucine-and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes, 59(10), 2426-2434.
  • Sahlin, K., Tonkonogi, M., & Söderlund, K. (1998). Energy supply and muscle fatigue in humans. Acta Physiologica Scandinavica, 162(3), 261-266.
  • Sakamoto, K., McCarthy, A., Smith, D., Green, K. A., Hardie, D. G., Ashworth, A., & Alessi, D. R. (2005). Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. The EMBO journal, 24(10), 1810-1820.
  • Sanders, M. J., Grondin, P. O., Hegarty, B. D., Snowden, M. A., & Carling, D. (2007). Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochemical Journal, 403(1), 139-148
  • Shaw, L. M. (2011). The insulin receptor substrate (IRS) proteins: at the intersection of metabolism and cancer. Cell Cycle, 10(11), 1750-1756.
  • Shen, L., Xiong, Y., Wang, D. Q., Howles, P., Basford, J. E., Wang, J., ... & Liu, M. (2013). Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats. Journal of lipid research, 54(5), 1430-1438.
  • Steinberg, G. R., McAinch, A. J., Chen, M. B., O’Brien, P. E., Dixon, J. B., Cameron-Smith, D., & Kemp, B. E. (2006). The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. The Journal of Clinical Endocrinology & Metabolism, 91(9), 3592-3597.
  • Świderska, E., Strycharz, J., Wróblewski, A., Szemraj, J., Drzewoski, J., & Śliwińska, A. (2018). Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake. In Glucose Transport. IntechOpen.
  • Ueda, M., Nishiumi, S., Nagayasu, H., Fukuda, I., Yoshida, K. I., & Ashida, H. (2008). Epigallocatechin gallate promotes GLUT4 translocation in skeletal muscle. Biochemical and biophysical research communications, 377(1), 286-290.
  • Watt, M. J., Dzamko, N., Thomas, W. G., Rose-John, S., Ernst, M., Carling, D., ... & Steinberg, G. R. (2006). CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nature medicine, 12(5), 541.
  • Wu, Y., Viana, M., Thirumangalathu, S., & Loeken, M. R. (2012). AMP-activated protein kinase mediates effects of oxidative stress on embryo gene expression in a mouse model of diabetic embryopathy. Diabetologia, 55(1), 245-254.
  • Xiao, B., Sanders, M. J., Underwood, E., Heath, R., Mayer, F. V., Carmena, D., ... & Saiu, P. (2011). Structure of mammalian AMPK and its regulation by ADP. Nature, 472(7342), 230.
  • Yagasaki, K. (2014). Anti-diabetic phytochemicals that promote GLUT4 translocation via AMPK signaling in muscle cells. Nutrition and Aging, 2(1), 35-44.
  • Zheng, J., & Ramirez, V. D. (2000). Inhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals. British journal of pharmacology, 130(5), 1115-1123.
  • Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., ... & Musi, N. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. The Journal of clinical investigation, 108(8), 1167-1174.
Toplam 66 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Cemalettin Kismiroğlu 0000-0002-9492-9069

Serdar Cengiz 0000-0002-9121-1262

Mustafa Yaman 0000-0001-9692-0204

Yayımlanma Tarihi 15 Nisan 2020
Yayımlandığı Sayı Yıl 2020 Sayı: 18

Kaynak Göster

APA Kismiroğlu, C., Cengiz, S., & Yaman, M. (2020). AMPK’nin Biyokimyası: Etki Mekanizmaları ve Diyabetin Tedavisindeki Önemi. Avrupa Bilim Ve Teknoloji Dergisi(18), 162-170. https://doi.org/10.31590/ejosat.676335