Document Type : Original Research


1 Divison of Veterinary Pathology, SKUAST-Kashmir, Srinagar, India

2 MRCSG, SKUAST-Kashmir, Srinagar, India

3 Divison of LPT, SKUAST-Kashmir, Srinagar, India


Background & Objectives: Alloxan & streptozotocin are used for inducing diabetic models. Their combination has been used to reduce the individual chemical dosage and minimize the side effects. Present investigation was aimed at studying pre-diabetic clinical changes induced by low doses of Alloxan-STZ cocktail in rabbits.
Methods: New Zealand White rabbits, 1-1.5 kg body weight, were administered alloxan (@50 mg/kg b.w.) and STZ (@ 35mg/kg b.w.) cocktail, as single intravenous dose. Blood glucose levels were monitored (0 h, 20 min, 1 h, and then hourly up to 9 h) and clinical signs noted. Rabbits surviving up to 9 hours were given glucose therapy.
Results: The cocktail caused immediate transient hypoglycaemia, followed by hyperglycaemia, and then progressively severe hypoglycaemia. Hypoglycaemia caused characteristic behavioural alterations from lethargy, through aesthesia, muscular weakness to recumbency. Severely affected rabbits revealed intermittent convulsions and died in coma.
 Conclusion: Low dose Alloxan-STZ cocktail induced triphasic immediate response in rabbits. The behavioural changes reflected glycaemic status serving as a guide for institution of glucose therapy.


  1. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: An overview. Indian J Med Res 2007; 125:451-72.
  2. Gorus FK, Malaisse WJ, Pipeleers DG. Selective uptake of alloxan by pancreatic B-cells. Bioch J 1982; 208(2):513–5.
  3. Szkudelski T. The mechanism of alloxan and streptozotocin action in β-cells of the rat pancreas. Physiol Res 2001; 50(6):536-46.
  4. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51(2):216–26.
  5. Kramer J, Moeller EL, Hachey A, Mansfield KG, Wachtman LM. Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates. Am J Physiol- Regul Integr Compar Physiol 2009; 296(3):R786-93.
  6. Mir SH, Darzi MM, Mir MS. Efficacy of Abroma augusta on biochemical and histomorphological features of Alloxan-induced diabetic rabbits. Iran J Pathol 2013; 8(3):143-8
  7. Elsner M, Tiedge M, Guldbakke B, Munday R, Lenzen S. Importance of the GLUT2 glucose transporter for pancreatic beta cell toxicity of alloxan. Diabetologia 2002; 45(11):1542–9.
  8. Mir MS, Darzi MM, Kamil SA, Khan HM. Clinical and pathomorphological effects of alloxan induced acute hypoglycaemia in rabbits. Proceedings of the 29th Annual Conference of IAVP and National Symposium On “Challenges in diagnostic pathology in domestic, pet, wild and aquatic animals” & Natl. Seminar on “Emerging trends in diagnosis and control of poultry diseases”; 2012 Nov. 5-7; Haryana, India. p. 84-5.
  9. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998; 47(2):224-9.
  10. Larsen MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O, Rolin B. Mild streptozotocin diabetes in the Gottingen minipig. A novel model of moderate insulin deficiency and diabetes. Am J Physiol - Endocrinol Metabol 2002; 282(6):E1342-51.
  11. Anderson HR, Stitt AW, Gardiner TA, Lloyd SJ, Archeri DB. Induction of alloxan/streptozotocin diabetes in dogs: A revised experimental technique. Lab Anm 1993; 27(3):281-5.
  12. Malaisse WJ, Doherty M, Ladriere L, Malaisse-Lagae F. Pancreatic uptake of [2-14C] alloxan. Int J Mol Med 2001; 7(3):311–5.
  13. Pocai A, Lam TKT, Gutierrez-Juarez R, Obici S, Schwartz GJ, Bryan J, et al. Hypothalamic KATP channels control hepatic glucose production. Nature 2005; 434(7036), 1026-31.
  14. Mythili MD, Vyas R, Akila G, Gunasekaran S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microscopy Res Tech 2004; 63(5):274–81.
  15. Park BH, Rho HW, Park JW, Cho CG, Kim JS, Chung HT, et al. Protective mechanism of glucose against alloxan-induced pancreatic beta-cell damage. Bioch Biophys Res Commun 1995; 210(1):1-6.
  16. Elsner M, Guldbakke B, Tiedge M, Munday R, Lenzen S. Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia 2000; 43(12):1528-33.
  17. Konrad RJ, Kudlow JE. The role of O-linked protein glycosylation in beta-cell dysfunction. Int J Mol Med 2002; 10(5):535–9.
  18. Pathak S, Dorfmueller HC, Borodkin VS, van Aalten DMF. Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic cell death. Chem Biol 2008; 15(8):799–807.
  19. Meier JJ, Kjems LL, Veldhuis JD, Lefèbvre P, Butler PC. Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis. Diabetes 2006; 55(4):1051–6.
  20. Sherwin RS. Bringing light to the dark side of insulin: A journey across the blood-brain barrier. Diabetes 2008; 57(9):2259–68.
  21. Paranjape SA, Chan O, Zhu1 W, Horblitt AM, McNay EC, Cresswell JA, et al. Influence of insulin in the ventromedial hypothalamus on pancreatic glucagon secretion in vivo. Diabetes 2010; 59(6):1521-7.
  22. Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 2002; 8(12):1376–82.
  23. Park MJ. Neuroendocrine mechanisms of behavioral changes induced by hypoglycemia. PhD Dissertation submitted to University of Illinois at Urbana-Champaign; 2008.
  24. Lin YY, Hsu CW, Sheu WHH, Chu SJ, Wu CP, Tsai SH. Risk factors for recurrent hypoglycemia in hospitalized diabetic patients admitted for severe hypoglycaemia. Yonsei Med J 2010; 51(3):367-74.
  25. Geddes J, Deary IJ, Frier BM. Effects of acute insulin-induced hypoglycaemia on psychomotor function: people with type 1 diabetes are less affected than non-diabetic adults. Diabetologia 2008; 51(10):1814-21.
  26. Guettier JM, Gorden P. Hypoglycemia. Endocrinol Metab Clin North Am 2006; 35(4):753-66.
  27. Arogyasami J, Sellers TL, Wilson GI, Jones JP, Duan C, Winder WW. Insulin-induced hypoglycemia in fed and fasted exercising rats. J Appl Physiol1992; 72(5):1991-8.