Persian Shallot (Allium hirtifolium Boiss) Extract Elevates Glucokinase (GCK) Activity and Gene Expression in Diabetic Rats
Mehdi Mahmoodi, Sadegh Zarei, Mohsen Rezaeian, Mohammad Kazemi Arababadi, Hassan Ghasemi, Hossein Khoramdelazad, Naser Rezayati, Gholamhossein Hasanshahi, Seyed-Mostafa Hosseini-Zijoud
Department of Biochemistry and Hamadan student research committee, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Social Medicine, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
DOI: 10.4236/ajps.2013.47170   PDF    HTML     6,352 Downloads   8,613 Views   Citations


Hepatic GCK is a key enzyme in glucose homeostasis and, as such, is a potential target for treatment strategies of diabetes. We investigated the effect of Persian shallot (Allium hirtifolium Boiss) hydroalchoholic extract on blood glucose level, plasma insulin level, GCK activity and its gene expression. Thirty two male rats were divided into 4 groups of 8, diabetic groups received 100 and 200 mg/kg Persian shallot extract, diabetic control and normal control received 0.9% saline for 30 days. Investigations of gene expression by Real-Time PCR showed that Persian shallot had led to gently increased GCK gene expression in diabetic rats. GCK activity increased significantly in Persian shallot treated group in dose dependent manner (P < 0.05). These results indicated that Persian shallot exhibited a significant potential as a hypoglycemic agent perhaps via its ability to enhance insulin secretion, GCK gene expression and its activity.

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M. Mahmoodi, S. Zarei, M. Rezaeian, M. Arababadi, H. Ghasemi, H. Khoramdelazad, N. Rezayati, G. Hasanshahi and S. Hosseini-Zijoud, "Persian Shallot (Allium hirtifolium Boiss) Extract Elevates Glucokinase (GCK) Activity and Gene Expression in Diabetic Rats," American Journal of Plant Sciences, Vol. 4 No. 7, 2013, pp. 1393-1399. doi: 10.4236/ajps.2013.47170.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. E. Gerich, “Clinical Significance, Pathogenesis, and Management of Postprandial Hyperglycemia,” Archives of Internal Medicine, Vol. 163, No. 11, 2003, pp. 13061316. doi:10.1001/archinte.163.11.1306
[2] R. P. Robertson, H. J. Zhang, K. L. Pyzdrowski and T. F. Walseth, “Preservation of Insulin mRNA Levels and Insulin Secretion in HIT Cells by Avoidance of Chronic Exposure to High Glucose Concentration,” Journal of Clinical Investigation, Vol. 90, No. 2, 1992, pp. 320-325. doi:10.1172/JCI115865
[3] T. Ferre, A. Pujol, E. Riu, F. Bosch and A. Valera, “Correction of Diabetic Alterations by Glucokinase,” Proceedings of the National Academy of Sciences, Vol. 93, No. 14, 1996, pp. 7225-7230. doi:10.1073/pnas.93.14.7225
[4] M. L. Cardenas, A. Cornish-Bowden and T. Ureta, “Evolution and Regulatory Role of the Hexokinases,” Biochimica et Biophysica Acta, Vol. 1401, No. 3, 1998, pp. 242-264. doi:10.1016/S0167-4889(97)00150-X
[5] F. M. Matschinsky, M. A. Magnuson, D. Zelent, T. L. Jetton, N. Doliba, Y. Han, R. Taub and J. Grimsby, “The Network of Glucokinase-Expressing Cells in Glucose Homeostasis and the Potential of Glucokinase Activators for Diabetes Therapy,” Diabetes, Vol. 55, No. 1, 2006, pp. 1-12. doi:10.2337/diabetes.55.01.06.db05-0926
[6] K. Kamata, M. Mitsuya, T. Nishimura, J. Eiki and Y. Nagata, “Structural Basis for Allosteric Regulation of the Monomeric Allosteric Enzyme Human Glucokinase,” Structure, Vol. 12, No. 3, 2004, pp. 429-438. doi:10.1016/j.str.2004.02.005
[7] P. Froguel, H. Zouali, N. Vionnet, G. Velho, M. Vaxillaire, F. Sun, S. Lesage, M. Stoffel, J. Takeda, P. Passa, et al., “Familial Hyperglycemia Due to Mutations in Glucokinase—Definition of a Subtype of Diabetes Mellitus,” The New England Journal of Medicine, Vol. 328, 1993, pp. 697-702. doi:10.1056/NEJM199303113281005
[8] F. J. Bourbonais, J. Chen, C. Huang, Y. W. Zhang, J. A. Pfefferkorn and J. A. Landro, “Modulation of Glucokinase by Glucose, Small Molecule Activator and Glucokinase Regulatory Protein: Steady-State Kinetic and Cell-Based Analysis,” Biochemical Journal Immediate Publication, 2011.
[9] P. B. Iynedjian, P. R. Pilot, T. Nouspikel, J. L. Milburn, C. Quaade, S. Hughes, C. Ucla and C. B. Newgard, “Differential Expression and Regulation of the Glucokinase Gene in Liver and Islets of Langerhans,” Proceedings of the National Academy of Sciences, Vol. 86, No. 20, 1989, pp. 7838-7842. doi:10.1073/pnas.86.20.7838
[10] M. A. Magnuson and K. D. Shelton, “An Alternate Promoter in the Glucokinase Gene Is Active in the Pancreatic Beta Cell,” The Journal of Biological Chemistry, Vol. 264, 1989, pp. 15936-15942. doi:10.1007/s11010-008-9719-3
[11] S. Celik and S. Erdogan, “Caffeic Acid Phenethyl Ester (CAPE) Protects Brain against Oxidative Stress and Inflammation Induced by Diabetes in Rats,” Molecular and Cellular Biochemistry, Vol. 312, No. 1-2, 2008, pp. 3946.
[12] L. Goldfrank, H. Lewin, N. Flomenbaum and M. A. Howland, “The Pernicious Panacea: Herbal Medicine,” Hospital Physician, Vol. 10, No. 10, 1982, pp. 64-86.
[13] M. C. Sabu, K. Smitha and K. Ramadasan, “Anti-Diabetic Activity of Green Tea Polyphenols and Their Role in Reducing Oxidative Stress in Experimental Diabetes,” Journal of Ethnopharmacology, Vol. 83, No. 1-2, 2002, pp. 109-116. doi:10.1016/S0378-8741(02)00217-9
[14] L. A. Mentz and E. P. Schenkel, “The Coherence and Reliability of Therapeutic Indications,” Notebook Farmacia, Vol. 5, 1989, pp. 93-119.
[15] U. Kopp, M. Cicha and M. Yorek, “Impaired Responsiveness of Renal Sensory Nerves in Streptozotocin-Treated Rats and Obese Zucker Diabetic Fatty Rats: Role of Angiotensin,” American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 294, No. 3, 2008, pp. 858-866. doi:10.1152/ajpregu.00830.2007
[16] N. Leelarungrayub, V. Rattanapanone, N. Chanarat and J. M. Gebicki, “Quantitative Evaluation of the Antioxidant Properties of Garlic and Shallot Preparations,” Nutrition, Vol. 22, No. 3, 2006, pp. 266-274. doi:10.1016/j.nut.2005.05.010
[17] J. Hosseini, S. M. Hosseini-Zijoud, F. Oubari, M. Mahmoodi, E. Abbasi Oshaghi, N. Rajabi Gilan, S. R. Ghasemi and B. Hashemi, “Hepatoprotective Effects of Hydroalcoholic Extract of Allium hirtifolium (Persian Shallot) in Diabetic Rats,” Journal of Basic and Clinical Physiology and Pharmacology, Vol. 23, No. 2, 2012, pp. 83-87.
[18] S.-M. Hosseini-Zijoud, J. Hosseini, M. Mahmoodi and H. Behrooz, “The Effects of Persian Shallot Extract on the Levels of Some Blood Biochemical Parameters in Streptozotocin-Induced Diabetic Rats,” African Journal of Agricultural Research, Vol. 7, No. 22, 2012, pp. 3308-3313. doi:10.5897/AJAR11.2498
[19] K. Lundgren, P. Jakobsen, M. Kristiansen, L. Norskov and L. Naerum, Patent No WO 97y09040-A1, 1997.
[20] W. H. Martin, D. J. Hoover, S. J. Armento, I. A. Stock, R. K. McPherson, D. E. Danley, R. W. Stevenson, et al. “Discovery of a Human Liver Glycogen Phosphorylase Inhibitor that Lowers Blood Glucose in Vivo,” Proceedings of the National Academy of Sciences, Vol. 95, No. 4, 1998, pp. 1776-1781. doi:10.1073/pnas.95.4.1776
[21] E. Strandelle, D. L. Eizirik, O. Korsgren, S. Sandler, “Functional Characteristics of Cultured Mouse Pancreatic Islets Following Exposure to Different Streptozotocin Concentrations,” Molecular Cell Endocrinology, Vol. 95, 1989, pp. 83-91.
[22] A. L. Davidson and W. J. Arion, “Factors Underlying Significant Underestimations of Glucokinase Activity in Crude Liver Extracts: Physiological Implications of Higher Cellular Activity,” Archives of Biochemistry and Biophysics, Vol. 253, No. 1, 1987, pp. 156-167. doi:10.1016/0003-9861(87)90648-5
[23] K. Seo-Yoon, K. Sung-Koo, L. Dong-Gyu, P. YoungGuk, L. Young-Choon, C. Ji-Chun and K. Cheorl-Ho, “Effect of Jindangwon on Streptozotocin-Induced Diabetes,” Life Sciences, Vol. 67, 2000, pp. 1251-1263.
[24] F. M. Matschinsky, Y. Liang, P. Kesaven, L. Wang, P. Froguel, G. Velho, D. Cohen, M. A. Permutt, Y. Tanizawa, T. L. Jetton, K. Niswender and M. A. Magnuson, “Glucokinase as Pancreatic Beta Cell Glucose Sensor and Diabetes Gene,” Journal of Clinical Investigation, Vol. 92, No. 5, 1993, pp. 2092-2098. doi:10.1172/JCI116809
[25] K. D. Shelton, A. J. Franklin, A. Khoor, J. Beechem and M. A. Magnuson, “Multiple Elements In the Upstream Glucokinase Promoter Contribute to Transcription in Insulinoma Cells,” Molecular and Cellular Biology, Vol. 12, 1992, pp. 4578-4589.
[26] J. E. Friedman, Y. Sun, T. Ishizuka, C. J. Farrell, S. E. McCormack, L. M. Herron, P. Hakimi, P. Lechner and J. S. Yun, “Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription and Hyperglycemia Are Regulated by Glucocorticoids in Genetically Obese db/db Transgenic Mice,” The Journal of Biological Chemistry, Vol. 272, 1997, pp. 31475-31481. doi:10.1074/jbc.272.50.31475
[27] S. Celika, S. Erdoganb and M. Tuzcuc, “Caffeic Acid Phenethyl Ester (CAPE) Exhibits Significant Potential as an Antidiabetic and Liver-Protective Agent in Streptozotocin-Induced Diabetic Rats,” Pharmacological Research, Vol. 60, No. 4, 2009, pp. 270-276. doi:10.1016/j.phrs.2009.03.017
[28] X. Zhang, W. Liang, Y. Mao, H. Li, Y. Yang and H. Tan, “Hepatic Glucokinase Activity Is the Primary Defect in Alloxan-Induced Diabetes of Mice,” Biomedicine & Pharmacotherapy, Vol. 63, No. 3, 2009, pp. 180-186. doi:10.1016/j.biopha.2007.07.006
[29] C. Postic, M. Shiota, K. D. Niswender, T. L. Jetton, Y. Chen, J. M. Moates, et al., “Dual roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic Beta Cell-Specific Gene Knock-Outs Using Cre Recombinase,” The Journal of Biological Chemistry, Vol. 274, 1999, pp. 305-315. doi:10.1074/jbc.274.1.305
[30] J. Grimsby, R. Sarabu, W. L. Corbett, N. E. Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, et al., “Allosteric Activators of Glucokinase: Potential Role In Diabetes Therapy,” Science, Vol. 301, No. 5631, 2003, pp. 370-373. doi:10.1126/science.1084073
[31] U. J. Jung, M. K. Lee, K. S. Jeong and M. S. Choi, “The Hypoglycemic Effects of Hesperidin and Naringin Are Partly Mediated by Hepatic Glucose-Regulating Enzymes in C57BL/KsJ-db/db Mice,” The Journal of Nutrition, Vol. 134, No. 10, 2004, pp. 2499-2503.
[32] E. K. Song, H. Hur and M. K. Han, “Epigal-locatechin Gallate Prevents Autoimmune Diabetes Induced by Multiple Low Doses of Streptozotocin in Mice,” Archives of Pharmacal Research, Vol. 26, No. 7, 2003, pp. 559-563. doi:10.1007/BF02976881
[33] Y.-G. Li, D.-F. Ji, S. Zhong, Z.-Q. Lv, T.-B. Lin and S. Chen, “Hybrid of 1-Deoxynojirimycin and Polysaccharide from Mulberry Leaves Treat Diabetes Mellitus by Activating PDX-1/Insulin-1 Signaling Pathway and Regulating the Expression of Glucokinase, Phosphoenolpyruvate Carboxykinase and Glucose-6-Phosphatase in Alloxan-Induced Diabetic Mice,” Journal of Ethnopharmacology, Vol. 134, 2011, pp. 961-970. doi:10.1016/j.jep.2011.02.009
[34] T. Nakagawa, T. Yokozawa, K. Terasawa, S. Shu and L. R. Juneja, “Protective Activity of Green Tea against Free Radicaland Glucose-Mediated Protein Damage,” Journal of Agricultural and Food Chemistry, Vol. 50, No. 8, 2002, pp. 2418-2422.

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