Dr Lindsay Brown, Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Queensland 4072, Australia. Email: [email protected]

Presented at the International Society for Heart Research and International Union of Physiological Societies World Congress Satellite Meeting, Models of Cardiovascular Disease, 2−4 September 2001, Brisbane, Australia.

Read the full text

About

PDF

Tools

Share a link

Email
Wechat
Bluesky

Abstract

Background: Diabetes in humans induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy. The most common animal model of human diabetes is streptozotocin (STZ)-induced diabetes in the rat.

Methods: This project assessed cardiovascular, ocular and neuropathic changes over a period of 24 weeks post STZ administration in rats.

Results: STZ-diabetic rats (n = 96) showed stable signs of diabetes (hyperglycaemia, increased water and food intake with no increase in bodyweight): 52% of untreated STZ-diabetic rats (n = 50) survived 24 weeks after STZ administration. STZ-diabetic rats were normotensive with slowly developing systolic and diastolic dysfunction and an increased ventricular stiffness. Ventricular action potential durations were markedly prolonged. STZ-diabetic rats developed stable tactile allodynia. Cataracts developed to presumed blindness at 16 weeks but proliferative retinopathy was not observed even after 24 weeks.

Conclusion: The chronic STZ-diabetic rat mimics many but not all of the chronic complications observed in the diabetic human. The chronic STZ-diabetic rat may be a useful model to test therapeutic approaches for amelioration of chronic diabetic complications in humans. (Heart, Lung and Circulation 2003; 12: 44−50)

References

1 Butler R, Macdonald TM, Struthers AD, Morris AD. The clinical implications of diabetic heart disease. Eur. Heart J. 1998; 19: 1617−27.
10.1053/euhj.1998.1284
CAS PubMed Web of Science® Google Scholar
2 Marks JB, Raskin P. Cardiovascular risk in diabetes. A brief review. J. Diabetes Complications 2000; 14: 108−15.
10.1016/S1056-8727(00)00065-9
CAS PubMed Web of Science® Google Scholar
3 Torffvit O, Agardh C-D. The prognosis for type 2 diabetic patients with heart disease. A 10-year observation study of 385 patients. J. Diabetes Complications 2000; 14: 301−306.
10.1016/S1056-8727(00)00117-3
CAS PubMed Web of Science® Google Scholar
4 Torffvit O, Agardh C-D. The impact of metabolic and blood pressure control on incidence and progression of nephropathy. A 10-year study of 385 type 2 diabetic patients. J. Diabetes Complications 2001; 15: 307−13.
10.1016/S1056-8727(01)00176-3
CAS PubMed Web of Science® Google Scholar
5 Voutilainen-Kaunisto RM, Terävirta ME, Uusitupa MIJ, Niskanen LK. Occurrence and predictors of retinopathy and visual acuity in type 2 diabetic patients and control subjects. 10-year follow-up from the diagnosis. J. Diabetes Complications 2001; 15: 24−33.
10.1016/S1056-8727(00)00126-4
CAS PubMed Web of Science® Google Scholar
6 Partanen J, Niskanen L, Lehtinen J, Mervaala E, Siitonen O, Uusitupa M. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 1995; 333: 89−94.
10.1056/NEJM199507133330203
CAS PubMed Web of Science® Google Scholar
7 Zimmet P, Boyko EJ, Collier GR, De Courten M. Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann. NY Acad. Sci. 1999; 892: 25−44.
10.1111/j.1749-6632.1999.tb07783.x
CAS PubMed Web of Science® Google Scholar
8 Dagogo-Jack S. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch. Int. Med. 1997; 157: 1802−17.
CAS PubMed Web of Science® Google Scholar
9 Anonymous. The dangerous toll of diabetes. http://www.diabetes.org/ada/facts.asp Accessed 20 April 2001.
Google Scholar
10 Valle T, Tuomilehto J, Eriksson J. Epidemiology of NIDDM in Europids. In: KGMM Alberti, P Zimmet, RA DeFronzo, H Keen (Eds). International Textbook of Diabetes Mellitus, 2nd edn. John Wiley & Sons, London, 1997, pp. 125−42.
Google Scholar
11 Tomlinson KC, Gardiner SM, Hebden RA, Bennett T. Functional consequences of streptozotocin-induced diabetes mellitus, with particular reference to the cardiovascular system. Pharmacol. Rev. 1992; 44: 103−50.
CAS PubMed Web of Science® Google Scholar
12 Qiang X, Satoh J, Sagara M et al. Inhibitory effect of troglitazone on diabetic neuropathy in streptozotocin-diabetic rats. Diabetologia 1998; 41: 1321−6.
10.1007/s001250051072
CAS PubMed Web of Science® Google Scholar
13 Cameron NE, Cotter MA. Diabetes causes an early reduction in autonomic ganglion blood flow in rats. J. Diabetes Complications 2001; 15: 198−202.
10.1016/S1056-8727(01)00149-0
CAS PubMed Web of Science® Google Scholar
14 Gilbert RE, Kelly DJ, Cox AJ et al. Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes. Diabetologia 2000; 43: 1360−67.
10.1007/s001250051539
CAS PubMed Web of Science® Google Scholar
15 Mifsud SA, Allen TJ, Bertram JF et al. Podocyte food process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade. Diabetologia 2001; 44: 878−82.
10.1007/s001250100561
CAS PubMed Web of Science® Google Scholar
16 Miric G, Dallemagne C, Endre Z, Margolin S, Taylor SM, , Brown L. Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats. Br. J. Pharmacol. 2001; 133: 687−94.
10.1038/sj.bjp.0704131
CAS PubMed Web of Science® Google Scholar
17 Brown L, Fenning A, Shek A, Burstow D. Reversal of cardiovascular remodeling with candesartan. J. Renin-Angiotensin-Aldosterone System 2001; 2: S141−7.
10.1177/14703203010020012501
CAS Web of Science® Google Scholar
18 Brown L, Fenning A, Chan V et al. Echocardiographic assessment of cardiac structure and function in rats. Heart, Lung and Circ. 2003; 11: 167−73 .
10.1046/j.1444-2892.2002.00148.x
Google Scholar
19 Brown L, Duce B, Miric G, Sernia C. Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system. J. Am. Soc. Nephrol. 1999; 10: S143−8.
CAS PubMed Web of Science® Google Scholar
20 Hoey A, Amos G, Wettwer E, Raven U. Differential effects of BDF 9148 and DPI 201−106 on action potential and contractility in rat and guinea pig myocardium. J. Cardiovasc. Pharmacol. 1994; 23: 907−15.
10.1097/00005344-199406000-00008
CAS PubMed Web of Science® Google Scholar
21 Calcutt NA, Chaplan SR. Spinal pharmacology of tactile allodynia in diabetic rats. Br. J. Pharmacol. 1997; 122: 1478−82.
10.1038/sj.bjp.0701538
CAS PubMed Web of Science® Google Scholar
22 Mitton KP, Dean PA, Dzialoszynski T, Xiong H, Sanford SE, Trevithick JR. Modelling cortical cataractogenesis. 13. Early effects on lens ATP/ADP and glutathione in the streptozotocin rat model of the diabetic cataract. Exper. Eye Res. 1993; 56: 187−98.
10.1006/exer.1993.1026
CAS PubMed Web of Science® Google Scholar
23 Wang DW, Kiyosue T, Shigematsu S, Arita M. Abnormalities of K⁺ and Ca²⁺ currents in ventricular myocytes from rats with chronic diabetes. Am. J. Physiol. 1995; 269: H1288−96.
CAS PubMed Web of Science® Google Scholar
24 Cagliero E. Characteristics and mechanisms of high-glucose induced overexpression of basement membrane components in cultured human endothelial cells. Diabetes 1991; 40: 102−9.
CAS PubMed Web of Science® Google Scholar
25 Yu DY, Cringle SJ, Su EN, Yu PK, Jerums G, Cooper ME. Pathogenesis and intervention strategies in diabetic retinopathy. Clin. Exper. Ophthalmol. 2001; 29: 164−6.
10.1046/j.1442-9071.2001.00409.x
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume12, Issue1

March 2003

Pages 44-50

The Streptozotocin-Diabetic Rat as a Model of the Chronic Complications of Human Diabetes

Abstract

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

The Streptozotocin-Diabetic Rat as a Model of the Chronic Complications of Human Diabetes

Abstract

References

Citing Literature

References

Related

Information