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Islet protection and amelioration of diabetes type 2 in Psammomys obesus by treatment with cannabidiol

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DOI: 10.4236/jdm.2012.21005    3,529 Downloads   6,480 Views  

ABSTRACT

Background and purpose: Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been shown by us, to have an anti-inflammatory effect in collagen-induced arthritis in DBA mice and in type 1 diabetes in NOD mice. As inflammation is a process involved in diabetes type 2, we administered CBD to Psammomys obesus (sand rats), a species which develops diabetes type 2 when fed high-energy (HE) diet, to investigate whether we can hinder the development of the disease. Experimental Approach: Male Psammomys obesus were kept on a high energy diet during the experiments. They were treated with CBD (i.p injection, 5 mg/kg, 5 times/week) for 4 weeks and kept (without CBD) for another 29 - 39 days. The weights of the animals as well as blood glucose and plasma insulin levels were determined and the morphology of the pancreatic islets was examined. Key results: CBD significantly reduced blood glucose levels in Psammomys obesus, without effecting body weight. Plasma insulin levels were significantly higher in the CBD-treated group. The most striking effect noted was the marked decrease of the destruction of pancreatic islets and beta cells. Conclusions and implications: CBD partially protects pancreatic islets and beta cells from destruction. CBD lowers significantly the blood glucose level and increases insulin level in Psammomys obesus with diabetes type 2, but does not lead to obesity. As CBD already has been administered to patients for other medical indications we propose its use as a therapeutic agent in diabetes type 2.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Ehud, Z. , Lola, W. , Itamar, R. , Natan, P. , Zhanna, Y. and Ruth, G. (2012) Islet protection and amelioration of diabetes type 2 in Psammomys obesus by treatment with cannabidiol. Journal of Diabetes Mellitus, 2, 27-34. doi: 10.4236/jdm.2012.21005.

References

[1] Pickup, J.C., Chusney, G.D., Thomas, S.M. and Burt, D. (2000) Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Science, 67, 291-300. doi:10.1016/S0024-3205(00)00622-6
[2] Mishima, Y., Kuyama, A., Tada, A., Takahashi, K., Ishioka, T. and Kibata, M. (2001) Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with Type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 52, 119-123. doi:10.1016/S0168-8227(00)00247-3
[3] Mavridis, G., Souliou, E., Diza, E., Symeonidis, G., Pastore, F., Vassiliou, A.M. and Karamitsos, D. (2008) Inflammatory cytokines in insulin-treated patients with type 2 diabetes. Nutrition, Metabolism & Cardiovascular Diseases, 18, 471-476. doi:10.1016/j.numecd.2007.02.013
[4] Izzo, A.A., Borrelli, F., Capasso, R., Di Matzo, V. and Mechoulam, R., (2009) Non-psychotropic plant cannabinpids: New therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences, 30, 515-527. doi:10.1016/j.tips.2009.07.006
[5] Ben Amar, M. (2006) Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology, 105, 1-25. doi:10.1016/j.jep.2006.02.001
[6] Mechoulam, R., Peters, M., Murillo-Rodriguez, E. and Hanus, L.O. (2007) Cannabidiol—Recent advances. Chemistry & Biodiversity, 4, 1678-1692. doi:10.1002/cbdv.200790147
[7] Klein, T.W., Newton, C., Larsen, K., Lu, L., Perkins, I., Nong, L. and Friedman, H. (2003) The Cannabinoid system and immune modulation. Journal of Leukocyte Biology, 74, 486-496. doi:10.1189/jlb.0303101
[8] Zurier, R.B. (2003) Prospects for Cannabinoids as anti-inflammatory agents. Journal of Cellular Biochemistry, 88, 462-466. doi:10.1002/jcb.10291
[9] Mbvundula, E.C., Rainsford, K.D. and Bunning, R.A. (2004) Cannabinoids in pain and inflammation. Inflammopharmacology, 12, 99-114. doi:10.1163/1568560041352275
[10] Watzl, B., Scuderi, P. and Watson, R.R. (1991) Influence of marijuana components (THC and CBD) on human mononuclear cell cytokine secretion in vitro. Advances in Experimental Medicine and Biology, 288, 63-70.
[11] Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S. and Gallily, R. (2006) Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity, 39, 143-151. doi:10.1080/08916930500356674
[12] Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., Gallily, R. (2008) Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology, 54, 244-249. doi:10.1016/j.neuropharm.2007.06.029
[13] Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R. and Feldmann, M. (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences of the United States of America, 97, 9561-9566. doi:10.1073/pnas.160105897
[14] Ziv, E., Kalman, R. and Shafrir, E. (2007) Psammomys obesus: Nutritionally induced insulin resistance, diabetes and beta cell loss. In: Shafrir, E., Ed., Animal Models of Diabetes, Second Edition, CRC Press, Boca Raton, 289-310.
[15] Gaoni, Y. and Mechoulam, R. (1971) The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. Journal of the American Chemical Society, 93, 217-224. doi:10.1021/ja00730a036
[16] Shafrir, E., Ziv, E. and Kalman, R. (2006) Nutritionally induced diabetes in desert rodants as models of type 2 diabetes: Acomys Cahirinus (Spiny mice) and Psammomys obesus (desert gerbil). ILAR Journal, 47, 212-224.
[17] Bar-On, H., Ben-Sasson, R., Ziv, E., Arar, N. and Shafrir, E. (1999) Irreversibility of nutritionally induced NIDDM in Psammomys obesus is related to β-cell apoptosis. Pancreas, 18, 259-265. doi:10.1097/00006676-199904000-00007
[18] Ziv, E., Kalman, R., Hershkop, K., Barash, V., Shafrir, E. and Bar-On, H. (1996) Insulin resistance in the NIDDM model Psammomys obesus in the normoglycaemic-normoinsilinaemic state. Diabetologia, 39, 1269-1275. doi:10.1007/s001250050569
[19] Donath, M.Y., Gross, D.J., Cerasi, E. and Kaiser, N. (1999) Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes, 48, 738-744. doi:10.2337/diabetes.48.4.738
[20] Patane, G., Piro, S., Rabuazzo, A.M., Anello, M., Vigneri, R. and Purrello, F. (2000) Metformin restores insulin secretion altered by chronic exposure to free fatty acids or high glucose: A direct metformin effect on pancreatic beta-cells. Diabetes, 49, 735-740. doi:10.2337/diabetes.49.5.735
[21] Pickup, J.C. (2004) Inflammation and activated innate immunity in the pathogenesis of type diabetes. Diabetes Care, 27, 813-823. doi:10.2337/diacare.27.3.813
[22] Wellen, K.E. and Hotamisligil, G.S. (2005) Inflammation, stress and Diabetes. Journal of Clinical Investigation, 115, 1111-1119.
[23] Marquie, G., Duhault, J., Espinal, J., Petkov, P., Jablenska, R., Khallayoun, S. and Bennani, N. (1997) S 15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus. Effect on pancreatic islets of insulin resistant animals. Cell and Molecular Biology (Noisy-le-grand), 43, 243-251.
[24] Shafrir, E., Spielman, S., Nachliel, I., Khamaisi, M., Bar-On, H. and Ziv, E. (2001) Treatment of diabetes with vanadium salts: general overview and amelioration of nutritionally induced diabetes in the Psammomys obesus gerbil. Diabetes/Metabolism Research and Reviews, 17, 55-66. doi:10.1002/1520-7560(2000)9999:9999<::AID-DMRR165>3.0.CO;2-J
[25] Hefetz, S., Ziv, E., J?rns, A., Lenzen, S. and Shafrir, E. (2006) Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus. Diabetes/ Metabolism Research and Reviews, 22,139-145. doi:10.1002/dmrr.583
[26] Sanigorski, A., Fahey, R., Cameron-Smith, D. and Collier, G.R. (2002) Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus. Diabetes, Obesity and Metabolism, 4, 346-350. doi:10.1046/j.1463-1326.2002.00216.x
[27] Anis, Y., Leshem, O., Reuveni, H., Wexler, I., Ben Sasson, R., Yahalom, B., Laster, M., Raz, I., Ben Sasson, S., Shafrir, E. and Ziv, E. (2004) Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes. Diabetologia, 47, 1232-1244. doi:10.1007/s00125-004-1444-1
[28] Shapira, M.Y., Appelbaum, Y.E., Hirshberg, B., Mizrahi, Y., Bar-On, H. and Ziv, E. (2000) A sustained, non-insulin related, hypoglycemic effect of electroacupuncture in diabetic Psammomys obesus. Diabetologia, 43, 809-813. doi:10.1007/s001250051379
[29] J?rns, A., Tiedge, M., Ziv, E., Shafrir, E. and Lenzen, S. (2002) Gradual loss of pancreatic beta-cell insulin, glucokinase and GLUT2 glucose transporter immunoreactivities during the time course of nutritionally induced type-2 diabetes in Psammomys obesus (sand rat). Virchows Archiv, 440, 63-69. doi:10.1007/s004280100490
[30] Like, A.A. and Miki, E. (1967) Diabetic syndrome in sand rats. IV. Morphologic changes in islet tissue. Diabetologia, 3, 143-166. doi:10.1007/BF01222192
[31] Rajesh, M., Mukhopadhyay, P., Batkai, S., Hasko, G., Lioudet, L., Drel, V.R., Obrosova, I.G. and Pacher, P. (2007) Cannabidiol attenuates high glucose induced endothelial cell inflammatory response and barrier disruption. American Journal of Physiology—Heart and Circulatory Physiology, 293, H610-H619. doi:10.1152/ajpheart.00236.2007
[32] Kaiser, N., Yuli, M., Uckaya, G., Oprescu, A.I., Berthault, M.F., Kargar, C,, Donath, M.Y., Cerasi, E. and Ktorza, A. (2005) Dynamic changes in {beta}-cell mass and pancreatic insulin during the evolution of nutrition-dependent diabetes in Psammomys obesus: Impact of glycemic control. Diabetes, 54, 138-145. doi:10.2337/diabetes.54.1.138
[33] Leibowitz, G., Yuli, M., Donath, M.Y., Nesher, R., Melloul, D., Cerasi, E., Gross, D.J. and Kaiser, N. (2001) Beta-cell glucotoxicity in the Psammomys obesus model of type 2 diabetes. Diabetes, 50, S113-S117. doi:10.2337/diabetes.50.2007.S113
[34] Plomgaard, P., Nielsen, A.R., Fischer, C.P., Mortensen, O.H., Broholm, C., Penkowa, M., Krogh-Madsen, R., Erikstrup, C., Lindegaard, B., Petersen, A.M., Taudorf, S. and Pedersen, B.K. (2007) Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia, 50, 2562-2571. doi:10.1007/s00125-007-0834-6
[35] Tsiotra, P.C., Tsigos, C., Yfanti, E., Anastasiou, E., Vikentiou, M., Psarra, K., Papasteriades, C. and Raptis, S.A. (2007) Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women. Hormone and Metabolic Research, 39, 758-763. doi:10.1055/s-2007-990288

  
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