ชมพู่ทับทิมจันทร์เพิ่มกระบวนการส่งสัญญาณของอินซูลินในตับของหนูเบาหวาน
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ม.ค. 5, 2020
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ชมพู่ทับทิมจันทร์ เบาหวาน ตับ กระบวนการส่งสัญญานของอินซูลิน
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บทคัดย่อ
การศึกษานี้มีวัตถุประสงค์เพื่อศึกษาผลของชมพู่ทับทิมจันทร์ [Syzygium samarangense (Blume) Merrill. & L.M. Perry var. Samarangense] ต่อกระบวนการส่งสัญญานของอินซูลินภายในตับของหนูเบาหวานเพศผู้ โดยหนี่ยวนำหนูขาวให้เป็นเบาหวานด้วยการฉีดสเตรปโทโซโทซิน (65 มิลลิกรัม/กิโลกรัม น้ำหนักตัว) เข้าทางช่องท้องแบบครั้งเดียว แล้วหนูเบาหวานจะได้รับการป้อนด้วยชมพู่ทับทิมจันทร์ ขนาด 100 มิลลิกรัม/กิโลกรัม น้ำหนักตัว/วัน เป็นเวลา 4 สัปดาห์ หลังจากนั้นศึกษาระดับน้ำตาลในเลือด การเกิด lipid peroxidation และการแสดงออกของโปรตีนที่เกี่ยวข้องกับการส่งสัญญาณของอินซูลินในตับด้วยเทคนิค Western blotting ผลการศึกษาพบว่าหนูเบาหวานมีระดับน้ำตาลในเลือดเพิ่มขึ้นอย่างมีนัยสำคัญทางสถิติเมื่อเปรียบเทียบกับหนูปกติ สอดคล้องกับระดับการแสดงออกของโปรตีน insulin receptor-β (InR-β), phospho-insulin receptor substrate 1 [p-IRS1 (Ser307)] และ phospho-JNK [p-JNK (Thr183/Tyr185)] ที่พบเพิ่มขึ้น ซึ่งบ่งชี้ถึงภาวะดื้อต่ออินซูลินที่ตับ นอกจากนี้ยังพบระดับของ malondialdehyde (MDA) เพิ่มขึ้นในตับของหนูเบาหวานด้วย อย่างไรก็ตามการให้ชมพู่ทับทิมจันทร์ (100 มิลลิกรัม/กิโลกรัม น้ำหนักตัว) แก่หนูเบาหวานพบว่าสามารถลดระดับน้ำตาลในเลือด การแสดงออกของโปรตีน InR- β, p-IRS1 (Ser307) และ p-JNK (Thr183/Tyr185) รวมทั้งระดับของ MDA ในตับของหนูเบาหวานอย่างมีนัยสำคัญทางสถิติ ดังนั้นผลการทดลองในการศึกษานี้จึงมีความเป็นไปได้ว่าชมพู่ทับทิมจันทร์สามารถช่วยเพิ่มกระบวนการส่งต่อสัญญานของอินซูลินภายในตับของหนูเบาหวาน ซึ่งสอดคล้องกับการลดลงของภาวะเครียดออกซิเดชันในเนื้อเยื่อตับของหนูเบาหวาน
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ประเภทบทความ
Medical Sciences
เอกสารอ้างอิง
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[15] McClain, D.A. and Crook, E.D., 1996, Hexosamines and insulin resistance, Diabetes 45: 1003-1009.
[16] Shulman, G.I., 2000, Cellular mechanisms of insulin resistance, J. Clin. Invest. 106: 171-176.
[17] Aguirre, V., Uchida, T., Yenush, L., Davis, R. and Whitei, M.F., 2000, The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307, J. Biol. Chem. 275: 9047-9054.
[18] Yang, R. and Trevillyan, J.M., 2008, c-Jun N-terminal kinase pathways in diabetes, Int. J. Biochem. Cell Biol. 40: 2702-2706.
[19] Khandaker, M.M. and Boyce, A.N., 2016, Growth, distribution and physiochemical properties of wax apple (Syzygium samarangense): A review, Aust. J. Crop Sci. 10: 1640-1648.
[20] Kuo, Y.C., Yang, L.M. and Lin, L.C., 2004, Isolation and immunomodulatory effect of flavonoids from Syzygium samara gense, Plant. Med. 70: 1237-1239.
[21] Nair, A.G.R., Krishnan, S., Ravikrishna, C. and Madhusudanan, K.P., 1999, New and rare flavonol glycosides from leaves of Syzygium samarangense, Fitoterapia 70: 148-151.
[22] Resurreccion-Magno, M.H., Villasenor, I.M., Harada, N. and Monde, K., 2005, Anti hyperglycaemic flavonoids from Syzygium samarangense (Blume) Merr. and Perry, Phytother. Res. 19: 246-251.
[23] Khandaker, M.M., Boyce, A.N., Osman, N. and Hossain, A.S., 2012, Physiochemical and phytochemical properties of wax apple (Syzygium samarangense [Blume] Merrill & L. M. Perry var. Jambu Madu) as affected by growth regulator application, Sci. World J. 2012: 728613.
[24] Srivastava, R., Shaw, A.K. and Kulshreshtha, D.K., 1995, Triterpenoids and chalcone from Syzygium samarangense, Phyto chemistry 38: 687-689.
[25] Shen, S.C. and Chang, W.C., 2013, Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet-induced diabetic rats, Food Chem. 136: 858-863.
[26] Shen, S.C., Chang, W.C. and Chang, C.L., 2012, Fraction from Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Fruit extract ameliorates insulin resistance via modulating insulin signaling and inflammation pathway in tumor necrosis factor α-treated FL83B mouse hepato cytes, Int. J. Mol. Sci. 13: 8562-8577.
[27] Khamchan, A., Paseephol, T. and Hanchang, W., 2018, Protective effect of wax apple [Syzygium samarangense (Blume) Merr. & L.M. Perry] against streptozotocin-induced pancreatic β-cell damage in diabetic rats, Biomed. Pharm. 108: 634-645.
[28] Goyal, S.N., Reddy, N.M., Patil, K.R., Nakhate, K.T., Ojha, S., Patil, C.R. and Agrawal, Y.O., 2016, Challenges and issues with streptozotocin-induced diabetes: A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics, Chem. Biol. Interact. 244: 49-63.
[29] Lenzen, S., 2008, The mechanisms of alloxan- and streptozotocin-induced diabetes, Diabetologia 51: 216-226.
[30] Boucher, J., Kleinridders, A. and Kahn, C.R., 2014, Insulin receptor signaling in normal and insulin-resistant states, Cold Spring Harb. Perspect. Biol. 6(1): a009191.
[31] Rains, J.L. and Jain, S.K., 2011, Oxidative stress, insulin signaling, and diabetes, Free Rad. Biol. Med. 50: 567-575.
[32] Boucher, J., Kleinridders, A. and Kahn, C.R., 2014, Insulin receptor signaling in normal and insulin-resistant states, Cold Spring Harb Perspect Biol. 6(1): a009191.
[33] Zhou, J., Xu, G., Bai, Z., Li, K., Yan, J., Li, F., Ma, S., Xu, H. and Huang, K., 2015, Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway, Toxicol. Appl. Pharm. 289: 409-418.
[34] Al-Attar, A.M. and Alsalmi, F.A., 2017, Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats, Saudi. J. Biol. Sci. 26: 118-128.
[35] Jayachandran, M., Zhang, T., Ganesan, K., Xu, B. and Chung, S.S.M., 2018, Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats, Eur. J. Pharm. 829: 112-120.
[36] Vinayagam, R., Jayachandran, M., Chung, S.S.M. and Xu, B., 2018, Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK/ACC signaling pathways in streptozotocin-induced diabetic rats, Biomed Pharm. 103: 1012-1017.
[37] Wei, Y., Gao, J., Qin, L., Xu, Y., Wang, D., Shi, H., Xu, T. and Liu, T., 2017, Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway, Biomed Pharm. 93: 352-358.
[38] Kadowaki, T., Kasuga, M., Akanuma, Y., Ezaki, O. and Takaku, F., 1984, Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats, J. Biol. Chem. 259: 14208-14216.
[39] Tozzo, E. and Desbuquois, B., 1992, Effects of STZ-induced diabetes and fasting on insulin receptor mRNA expression and insulin receptor gene transcription in rat liver, Diabetes 41: 1609.
[40] Vinayagam, R. and Xu, B., 2015, Antidiabetic properties of dietary flavonoids: A cellular mechanism review, Nutr. Metab. (Lond). 12: 60.
[41] Yang, L., Wang, Z., Jiang, L., Sun, W., Fan, Q. and Liu, T., 2017, Total flavonoids extracted from Oxytropis falcata Bunge improve insulin resistance through regulation on the IKKβ/NF-κB inflammatory pathway, Evid. Based Complementary Altern Med. 2017: 2405124.
[42] M., S.S. and C., D.N., 2017, Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats, Biomed Pharma. 94: 605-611.
[43] Zhang, Z.F., Lu, J., Zheng, Y.L., Wu, D.M., Hu, B., Shan, Q., Cheng, W., Li, M.Q. and Sun, Y.Y., 2013, Purple sweet potato color attenuates hepatic insulin resistance via blocking oxidative stress and endoplasmic reticulum stress in high-fat-diet-treated mice, J. Nutr. Biochem. 24: 1008-1018.
[44] Kim, Y.J., Kim, H.C., Ko, H., Amor, E.C., Lee, J.W. and Yang, H.O., 2012, Inhibitory effects of aurentiacin from Syzygium samarangense on lipopolysaccharide-induced inflammatory response in mouse macrophages, Food Chem. Toxicol. 50: 1027-1035.
[45] Shen, S.C., Chang, W.C. and Chang, C.L., 2013, An extract from wax apple [Syzygium samarangense (Blume) Merrill & Perry] effects glycogenesis and glycolysis pathways in tumor necrosis factor-alpha-treated FL83B mouse hepatocytes, Nutrients 5: 455-467.
[2] American Diabetes Association, 2009, Diagnosis and classification of diabetes mellitus, Diab. Care 32: 62-67.
[3] Forbes, J.M. and Cooper, M.E., 2013, Mechanisms of diabetic complications, Physiol. Rev. 93: 137-188.
[4] Wilcox, G., 2005, Insulin and insulin resistance, Clin. Biochem. Rev. 26: 19-39.
[5] Postic, C., Dentin, R. and Girard, J., 2004, Role of the liver in the control of carbohydrate and lipid homeostasis, Diab. Metab. 30: 398-408.
[6] Rui, L., 2014, Energy metabolism in the liver, Compr. Physiol. 4: 177-197.
[7] Edgerton, D.S., Kraft, G., Smith, M., Farmer, B., Williams, P.E., Coate, K.C., Printz, R.L., O’Brien, R.M. and Cherrington, A.D., 2017, Insulin’s direct hepatic effect explains the inhibition of glucose production caused by insulin secretion, JCI Insight 2: 91863.
[8] Parveen, K., Khan, M.R., Mujeeb, M. and Siddiqui, W.A., 2010, Protective effects of Pycnogenol® on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats, Chem. Biol. Interact. 186: 219-227.
[9] Trauner, M., Arrese, M. and Wagner, M., 2010, Fatty liver and lipotoxicity, Biochim. Biophys. Acta 1801: 299-310.
[10] Meshkani, R. and Adeli, K., 2009, Hepatic insulin resistance, metabolic syndrome and cardiovascular disease, Clin. Biochem.
42: 1331-1346.
[11] Adiels, M., Taskinen, M.R. and Boren, J., 2008, Fatty liver, insulin resistance, and dyslipidemia, Curr. Diab. Rep. 8: 60-64.
[12] King, G.L. and Loeken, M.R., 2004, Hyperglycemia-induced oxidative stress in diabetic complications, Histochem. Cell Biol. 122: 333-338.
[13] Tomas, E., Lin, Y.S., Dagher, Z., Saha, A., Luo, Z., Ido, Y. and Ruderman, N.B., 2002, Hyperglycemia and insulin resistance: Possible mechanisms, Ann. N Y Acad. Sci. 967: 43-51.
[14] Buse, M.G., 2006, Hexosamines, insulin resistance, and the complications of diabetes: current status, Am. J. Physiol. Endocrinol. Metab. 290: 1-8.
[15] McClain, D.A. and Crook, E.D., 1996, Hexosamines and insulin resistance, Diabetes 45: 1003-1009.
[16] Shulman, G.I., 2000, Cellular mechanisms of insulin resistance, J. Clin. Invest. 106: 171-176.
[17] Aguirre, V., Uchida, T., Yenush, L., Davis, R. and Whitei, M.F., 2000, The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307, J. Biol. Chem. 275: 9047-9054.
[18] Yang, R. and Trevillyan, J.M., 2008, c-Jun N-terminal kinase pathways in diabetes, Int. J. Biochem. Cell Biol. 40: 2702-2706.
[19] Khandaker, M.M. and Boyce, A.N., 2016, Growth, distribution and physiochemical properties of wax apple (Syzygium samarangense): A review, Aust. J. Crop Sci. 10: 1640-1648.
[20] Kuo, Y.C., Yang, L.M. and Lin, L.C., 2004, Isolation and immunomodulatory effect of flavonoids from Syzygium samara gense, Plant. Med. 70: 1237-1239.
[21] Nair, A.G.R., Krishnan, S., Ravikrishna, C. and Madhusudanan, K.P., 1999, New and rare flavonol glycosides from leaves of Syzygium samarangense, Fitoterapia 70: 148-151.
[22] Resurreccion-Magno, M.H., Villasenor, I.M., Harada, N. and Monde, K., 2005, Anti hyperglycaemic flavonoids from Syzygium samarangense (Blume) Merr. and Perry, Phytother. Res. 19: 246-251.
[23] Khandaker, M.M., Boyce, A.N., Osman, N. and Hossain, A.S., 2012, Physiochemical and phytochemical properties of wax apple (Syzygium samarangense [Blume] Merrill & L. M. Perry var. Jambu Madu) as affected by growth regulator application, Sci. World J. 2012: 728613.
[24] Srivastava, R., Shaw, A.K. and Kulshreshtha, D.K., 1995, Triterpenoids and chalcone from Syzygium samarangense, Phyto chemistry 38: 687-689.
[25] Shen, S.C. and Chang, W.C., 2013, Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet-induced diabetic rats, Food Chem. 136: 858-863.
[26] Shen, S.C., Chang, W.C. and Chang, C.L., 2012, Fraction from Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Fruit extract ameliorates insulin resistance via modulating insulin signaling and inflammation pathway in tumor necrosis factor α-treated FL83B mouse hepato cytes, Int. J. Mol. Sci. 13: 8562-8577.
[27] Khamchan, A., Paseephol, T. and Hanchang, W., 2018, Protective effect of wax apple [Syzygium samarangense (Blume) Merr. & L.M. Perry] against streptozotocin-induced pancreatic β-cell damage in diabetic rats, Biomed. Pharm. 108: 634-645.
[28] Goyal, S.N., Reddy, N.M., Patil, K.R., Nakhate, K.T., Ojha, S., Patil, C.R. and Agrawal, Y.O., 2016, Challenges and issues with streptozotocin-induced diabetes: A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics, Chem. Biol. Interact. 244: 49-63.
[29] Lenzen, S., 2008, The mechanisms of alloxan- and streptozotocin-induced diabetes, Diabetologia 51: 216-226.
[30] Boucher, J., Kleinridders, A. and Kahn, C.R., 2014, Insulin receptor signaling in normal and insulin-resistant states, Cold Spring Harb. Perspect. Biol. 6(1): a009191.
[31] Rains, J.L. and Jain, S.K., 2011, Oxidative stress, insulin signaling, and diabetes, Free Rad. Biol. Med. 50: 567-575.
[32] Boucher, J., Kleinridders, A. and Kahn, C.R., 2014, Insulin receptor signaling in normal and insulin-resistant states, Cold Spring Harb Perspect Biol. 6(1): a009191.
[33] Zhou, J., Xu, G., Bai, Z., Li, K., Yan, J., Li, F., Ma, S., Xu, H. and Huang, K., 2015, Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway, Toxicol. Appl. Pharm. 289: 409-418.
[34] Al-Attar, A.M. and Alsalmi, F.A., 2017, Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats, Saudi. J. Biol. Sci. 26: 118-128.
[35] Jayachandran, M., Zhang, T., Ganesan, K., Xu, B. and Chung, S.S.M., 2018, Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats, Eur. J. Pharm. 829: 112-120.
[36] Vinayagam, R., Jayachandran, M., Chung, S.S.M. and Xu, B., 2018, Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK/ACC signaling pathways in streptozotocin-induced diabetic rats, Biomed Pharm. 103: 1012-1017.
[37] Wei, Y., Gao, J., Qin, L., Xu, Y., Wang, D., Shi, H., Xu, T. and Liu, T., 2017, Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway, Biomed Pharm. 93: 352-358.
[38] Kadowaki, T., Kasuga, M., Akanuma, Y., Ezaki, O. and Takaku, F., 1984, Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats, J. Biol. Chem. 259: 14208-14216.
[39] Tozzo, E. and Desbuquois, B., 1992, Effects of STZ-induced diabetes and fasting on insulin receptor mRNA expression and insulin receptor gene transcription in rat liver, Diabetes 41: 1609.
[40] Vinayagam, R. and Xu, B., 2015, Antidiabetic properties of dietary flavonoids: A cellular mechanism review, Nutr. Metab. (Lond). 12: 60.
[41] Yang, L., Wang, Z., Jiang, L., Sun, W., Fan, Q. and Liu, T., 2017, Total flavonoids extracted from Oxytropis falcata Bunge improve insulin resistance through regulation on the IKKβ/NF-κB inflammatory pathway, Evid. Based Complementary Altern Med. 2017: 2405124.
[42] M., S.S. and C., D.N., 2017, Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats, Biomed Pharma. 94: 605-611.
[43] Zhang, Z.F., Lu, J., Zheng, Y.L., Wu, D.M., Hu, B., Shan, Q., Cheng, W., Li, M.Q. and Sun, Y.Y., 2013, Purple sweet potato color attenuates hepatic insulin resistance via blocking oxidative stress and endoplasmic reticulum stress in high-fat-diet-treated mice, J. Nutr. Biochem. 24: 1008-1018.
[44] Kim, Y.J., Kim, H.C., Ko, H., Amor, E.C., Lee, J.W. and Yang, H.O., 2012, Inhibitory effects of aurentiacin from Syzygium samarangense on lipopolysaccharide-induced inflammatory response in mouse macrophages, Food Chem. Toxicol. 50: 1027-1035.
[45] Shen, S.C., Chang, W.C. and Chang, C.L., 2013, An extract from wax apple [Syzygium samarangense (Blume) Merrill & Perry] effects glycogenesis and glycolysis pathways in tumor necrosis factor-alpha-treated FL83B mouse hepatocytes, Nutrients 5: 455-467.
