Effect of Streptozotocin-Induced Diabetes on Bone and Heart Development in Juvenile Rats

  • Kim, Joo-Heon (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Lee, Young-Jeon (Department of Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University) ;
  • Lee, Sang-Un (Department of Physical Therapy, Aomori University of Health and Welfare) ;
  • Suzuki, Takao (Department of Physical Therapy, Aomori University of Health and Welfare) ;
  • Lee, Sang-Kil (Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University) ;
  • Kang, Tae-Young (College of Veterinary Medicine, Jeju National University) ;
  • Hong, Yong-Geun (Department of Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University)
  • Received : 2010.05.07
  • Accepted : 2010.06.23
  • Published : 2010.06.30

Abstract

Our objective of current study was to investigate the development of bone and heart in association with diabetes mellitus (DM). DM was induced by administering an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) to 4-week-old Sprague-Dawley rats. Body weight and blood glucose were monitored, and rats were sacrificed after 2 or 5 weeks. The left ventricle (LV), including the interventricular septum, was weighed, and body weight and tibial bone length were assessed. Young diabetic rats showed reduced growth in terms of tibial length and body weight compared to controls. Moreover, diabetic males showed more significant growth suppression and reduced LV size than diabetic females. Morphometric analysis of tibiae from diabetic rats revealed suppressed bone growth at 2 and 5 weeks, with no difference between genders. STZ-induced diabetes decreased bone growth and retarded pre-pubertal heart development. As a result, diabetes may increase cardiovascular risk factors and lead to eventual heart failure. Therefore, new therapeutic approaches are required for diabetic children exhibiting growth retardation. Heart growth factor, exercise, and cardiopulmonary physical therapy may be required to promote heart development and physiological function.

Keywords

Acknowledgement

Supported by : Rural Development Administration

References

  1. Al-Qadreh A, Voskaki I, Kassiou C, Athanasopoulou H, Sarafidou E, Bartsocas CS (1996): Treatment of osteopenia in children with insulin-dependent diabetes mellitus: the effect of 1 alphaphydroxyvitamin $D_{3}$. Eur J Pediatr 155:15-17. https://doi.org/10.1007/BF02309849
  2. Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire A, de Groote P (2003): Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol 2(1):1-16. https://doi.org/10.1186/1475-2840-2-1
  3. Blaas L, Kornfeld JW, Schramek D, Musteanu M, Zollner G, Gumhold J, van Zijl F, Schneller D, Esterbauer H, Egger G, Mair M, Kenner L, Mikulits W, Eferl R, Moriggl R, Penniger J, Trauner M, Casanova E (2010): Disruption of the growth hormone-signal transducer and activator of transcription 5-insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasis. Hepatology 51(4):1319-1326. https://doi.org/10.1002/hep.23469
  4. Chiarelli F, Giannini C, Mohn A (2004): Growth, growth factors and diabetes. Eur J Endocrinol 151:U109-U117. https://doi.org/10.1530/eje.0.151U109
  5. Cortright RN, Colins HL, Chandler MP, Lemon PW, DiCarlo SE (1996): Diabetes reduces growth and body composition more in male than in female rats. Physiol Behav 60(5):1233-1238. https://doi.org/10.1016/S0031-9384(96)00222-3
  6. Devereux RB, Roman MJ, Paranicas M, O'Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000): Impact of diabetes on cardiac structure and function: the Strong Heart Study. Circulation 101:2271-2276. https://doi.org/10.1161/01.CIR.101.19.2271
  7. Donaghue KC, Kordonouri O, Chan A, Silink M (2003): Secular trends in growth in diabetes: are we winning? Arch Dis Child 88(2):151-154. https://doi.org/10.1136/adc.88.2.151
  8. Dunger D, Ahmed L, Ong K (2002): Growth and body composition in type 1 diabetes mellitus. Horm Res 58:66-71. https://doi.org/10.1159/000064762
  9. Factor SM, Borczuk A, Charron MJ, Fein FS, van Hoeven KH, Sonnenblick EH (1996): Myocardial alterations in diabetes and hypertension. Diabetes Res Clin Pract 31(Suppl):S133-S142.
  10. Fonarow GC (2005): An approach to heart failure and diabetes mellitus. Am J Cardiol 96(4A):47E-52E.
  11. Ho KK, Pinsky JL, Kannel WB, Levy D (1993): The epidemiology of heart failure: the Framingham study. J Am Coll Cardiol 22:6A-13A. https://doi.org/10.1016/0735-1097(93)90455-A
  12. Isgaard J (2004): Cardiovascular disease and risk factors: the role of growth hormone. Horm Res 62(4):31-38. https://doi.org/10.1159/000080906
  13. Maor G, Karnieli E (1999): The insulin-sensitive glucose transporter (GLUT4) is involved in early bone growth in control and diabetic mice, but is regulated through the insulin-like growth factor I receptor. Endocrinology 140(4):1841-1851. https://doi.org/10.1210/en.140.4.1841
  14. Maor G, Laron Z, Eshet R, Silbermann M (1993): The early postnatal development of the murine mandibular condyle is regulated by endogenous insulin-like growth factor-I. J Endocrinol 137(1):21-26. https://doi.org/10.1677/joe.0.1370021
  15. Palmieri V, Bella JN, Amett DK, Liu JE, Oberman A, Schuck MY, Kitzman DW, Hopkins PN, Morgan D, Rao DC, Devereux RB (2001): Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects. The Hypertension Genetic Epidemiology Network (HyperGEN) study. Circulation 103:102-107. https://doi.org/10.1161/01.CIR.103.1.102
  16. Palmieri V, Tracy RP, Roman MJ, Liu JE, Best LG, Bella JN, Robbins DC, Howard BV, Devereux RB (2003): Relation of left ventricular hypertrophy to inflammation and alburninuria in adults with type 2 diabetes: the strong heart study. Diabetes Care 26:2764-2769. https://doi.org/10.2337/diacare.26.10.2764
  17. Reinehr T, Kleber M, de Sousa G, Andler W (2009): Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention. Int J Pediatr Obes 4(4):215-223. https://doi.org/10.3109/17477160902952464
  18. Rolland YM, Perry HM 3rd, Patrick P, Banks WA, Morley JE (2006): Leptin and adiponectin levels in middle-aged postmenopausal women: associations with lifestyle habits, hormones, and inflammatory markers--a cross-sectional study. Metabolism 55(12):1630-1636. https://doi.org/10.1016/j.metabol.2006.07.026
  19. Salemo M, Amabile G, Mandato C, Di Maio S, Lecora M, Avvedimento EV, Andria G (2003): Growth retardation, developmental delay, distinctive face, multiple endocrine abnormalities, and adenylyl cyclase dysfunction: a new syndrome? Am J Med Genet A 120A(3):389-94. https://doi.org/10.1002/ajmg.a.20107
  20. Solang L, Malmberg K, Ryden L (1999): Diabetes mellitus and congestive heart failure. Further knowledge needed. Eur Heart J 20:789-795. https://doi.org/10.1053/euhj.1998.1472
  21. Sowers JR (2004): Treatment of hypertension in patients with diabetes. Arch Intern Med 164:1850-1857. https://doi.org/10.1001/archinte.164.17.1850
  22. Ryden L, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Packer M, Poole-Wilson PA (2000): Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J 21:1967-1978. https://doi.org/10.1053/euhj.2000.2311
  23. Taverna MJ, M'Bemba J, Sola A, Chevalier A, Slama G, Selam JL (2000): Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes. Diabetes Metab 26(1):58-64.
  24. Thebault S, Hoenderop JG, Bindels RJ (2006): Epithelial $Ca^{2+}$ and $Mg^{2+}$ channels in kidney disease. Adv Chronic Kidney Dis 13(2):110-117. https://doi.org/10.1053/j.ackd.2006.01.002
  25. Vanelli M, de Fanti A, Adinolfi B, Ghzzoni L (1992): Oinical data regarding the growth of diabetic cildren. Horm Res 37(3):65-69. https://doi.org/10.1159/000182404
  26. Verhaeghe J, van Bree R, van Herck E, Rummens K, Vercruysse L, Bouillon R, Pijnenborg R (1999): Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation. Pediatr Res 45(2):209-217. https://doi.org/10.1203/00006450-199902000-00009