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Journal Technologies of Living Systems №9 for 2013 г.
Article in number:
Activity of adenylyl cyclase system in the myocardium and testes of rats with acute and long-term streptozotocin models of diabetes mellitus
Keywords: adenylyl cyclase adrenergic agonist myocardium relaxin testes somatostatin streptozotocin diabetes
Authors:
K.V. Derkach - Ph.D.(Biol.), Researcher Scientific, Institute of Evolutionary Physiology and Biochemistry n.a. I.M. Sechenov, Russian Academy of Sciences (St.Petersburg)
I.V. Moyseyuk - Post-graduate Student, Institute of Evolutionary Physiology and Biochemistry n.a. I.M. Sechenov, Russian Academy of Sciences (St.Petersburg)
O.V. Chistyakova - Ph.D.(Biol.), Senior Researcher Scientific, Institute of Evolutionary Physiology and Biochemistry n.a. I.M. Sechenov, Russian Academy of Sciences (St.Petersburg)
V.M. Bondareva - Ph.D.(Biol.), Leading Researcher Scientific, Institute of Evolutionary Physiology and Biochemistry n.a. I.M. Sechenov, Russian Academy of Sciences (St.Petersburg)
A.O. Shpakov - Dr.Sc.(Biol.), Head of Laboratory, Institute of Evolutionary Physiology and Biochemistry n.a. I.M. Sechenov, Russian Academy of Sciences (St.Petersburg)
Abstract:
To model the type 1 diabetes mellitus (T1DM) the acute streptozotocin rat model of T1DM induced by a single injection of streptozotocin at the dose 65 mg/kg is commonly used. The main disadvantage of this model is the rapid increase of metabolic abnormalities, which at the early stages of T1DM induces severe disturbances of physiological and biochemical processes and results in the death of the animals. We developed long-term, mild, model of T1DM induced by three injections of streptozotocin at the doses 40, 35 and 30 mg/kg on the first, 10th and 80th days of experiment. This model is closer to human T1DM than acute model, does not lead to the death of the animals in the first six months of disease and can be used successfully to the study of T1DM complications. According to out hypothesis, the alterations in adenylyl cyclase signaling system (ACSS) involved in the regulation of many cellular processes and subjected the greatest changes in diabetes is one of the key causes of T1DM complications. The purpose of the work is a comparative investigation of the changes of the basal and hormone- and non-hormonal agents-stimulated adenylyl cyclase (AC) activities in the myocardium and testes of rats with the acute (10- and 30-days-duration) and long-term (75- and 210-days-duration) streptozotocin models of T1DM. The body weight of rats with the acute model of T1DM was significantly decreased (after 10 and 30 days by 85 and 77 % compared with control), while in long-term T1DM the body weight decline was less pronounced. Glucose concentration in rats with the acute model was increased to 17-19 mM, in rats with long-term model 9 days after the first injection of streptozotocin glucose concentration was increased to 11 mM, 19 days after the second injection to 13 mM and further changes weakly. Insulin concentration in rats with the acute and long-term models was 0.1-0.2 and 0.4-0.5 ng/mL, respectively. In the myocardium of rats with the acute model of T1DM the basal AC activity was higher compared with control, and in rats with long-term model the activity was significantly decreased. In the testes of rats with the acute (30 days) and long-term (210 days) T1DM both basal and forskolin-stimulated AC activity was decreased. In both tissues the simulation of the enzyme by guanine nucleotides was weakened, and in the testes at early stages and in the myocardium at the later sages of T1DM. Among hormones, AC stimulators, AC effects of relaxin (myocardium), gonadotropin, PACAP-38 and isoproterenol (testes) were most attenuated. The difference between the models of T1DM was observed in the case of AC stimulating effects of adrenergic agonists, isoproterenol and noradrenaline, in the myocardium. In rats with the acute model they were first increased (10 days) and then decreased below the control level (30 days), while in rats with long-term T1DM these effects were decreased in both periods of disease. The significant decrease of AC inhibitory effects of somatostatin (both tissues) and noradrenaline (myocardium) was detected in both models of T1DM. Thus, the alterations in ACSS in the myocardium and testes of rats with the acute and long-term models of T1DM identified by us may be one of the key mechanisms underlying the etiology and pathogenesis of T1DM complications of the cardiovascular and reproductive systems.
Pages: 3-12
References

  1. Tesch G.H., Allen T.J. Rodent models of streptozotocin-induced diabetic nephropathy // Nephrology (Carlton). 2007. V. 12. P. 261-266.
  2. Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat: characteristics of the experimental model // Exp. Biol. Med. 2012. V. 237. P. 481-490.
  3. Lukic M.L., Stosic-Grujicic S., Shahin A. Effector mechanisms in low-dose streptozotocin-induced diabetes // Dev. Immunol. 1998. V. 6. R. 119-128.
  4. Tesch G.H., Allen T.J. Rodent models of streptozotocin-induced diabetic nephropathy // Nephrology. 2007. V. 12. P. 261-266.
  5. Shpakov A., Chistyakova O., Derkach K., Bondareva V. Hormonal signaling systems of the brain in diabetes mellitus // Neurodegenerative Diseases (Ed. by R.C. Chang), Intech Open Access Publisher. Rijeka, Croatia. 2011. P. 349-386.
  6. Shpakov A.O. Alterations in hormonal signaling systems in diabetes mellitus: origin, causality and specificity // Endocrinol. Metab. Syndrome. 2012. V. 1. DOI: 2161-1017-1-e106.
  7. Dincer U.D., Bidasee K.R., Guner S. et al. The effect of diabetes on expression of β1-, β2- and β3-adrenoreceptors in rat hearts // Diabetes. 2001. V. 50. P. 455-461.
  8. Hashim S., Li Y., Anand-Srivastava M.B. G protein-linked cell signaling and cardiovascular functions in diabetes/hyperglycemia // Cell. Biochem. Biophys. 2006. V. 44. P. 51-64.
  9. Shpakov A.O., Kuzneczova L.A., Plesneva S.A. i dr. Identifikacziya narushenij v gormono­chuvstvitel'noj AC-sisteme v tkanyax kry's s diabetom 1-go i 2-go tipov s ispol'zovaniem funkczional'ny'x zondov i sinteticheskix nanorazmerny'x peptidov // Texnologii zhivy'x sistem. 2007. T. 4. № (5-6). S. 96-108.
  10. Altan V.M., Arioglu E., Guner S., Ozcelikay A.T. The influence of diabetes on cardiac (-adre­no­ceptor subtypes // Heart Fail. Rev. 2007. V. 12. P. 58-65.
  11. Shpakov A.O., Chistyakova O.V., Derkach K.V. et al. Intranasal insulin affects adenylyl cyclase system in rat tissues in neonatal diabetes // Central Eur. J. Biol. 2012. V. 7. P. 33-47.
  12. Shpakov A.O., Derkach K.V., Chistyakova O.V. et al. The brain adenylyl cyclase signaling system and cognitive functions in rat with neonatal diabetes under the influence of intranasal serotonin // J. Metab. Syndrome, 2012. V. 1. http://dx.DOI.org/10.4172/jms.1000104.
  13. Shpakov A.O., Kuzneczova L.A., Ples­neva S.A., Perczeva M.N. Moleku­lyarny'e mexanizmy' izmeneniya chuv­stvitel'nosti adenilatcziklaznoj signal'noj sistemy' k biogenny'm aminam pri streptozotoczinovom diabete // Byullyuten' e'ksperimental'noj biologii i medicziny'. 2005. T. 140 (9). S. 286-290.
  14. Dobrin J.S., Lebeche D. Diabetic cardiomyopathy: signaling defects and therapeutic approaches // Expert. Rev. Cardiovasc. Ther. 2010. V. 8. P. 373-391.
  15. La Vignera S., Condorelli R., Vicari E. et al. Diabetes mellitus and sperm parameters // J. Androl. 2012. V. 33. P. 145-153.
  16. Schoeller E.L., Schon S., Moley K.H. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis // Cell Tissue Res. 2012. V. 349. P. 839-847.
  17. Snell-Bergeon J.K., Wadwa R.P. Hypoglycemia, diabetes, and cardiovascular disease // Diabetes Technol. Ther. 2012. V. 14 (Suppl 1). P. S51-S58.
  18. Shpakov A.O., Shpakova E.A., Tarasenko I.I., Derkach K.V. Reczeptornaya i tkanevaya speczi­fichnost' dejstviya peptidov, proizvodny'x czitoplazmaticheskix uchastkov reczeptorov serpantinnogo tipa // Biologicheskie membrany'. 2011. T. 28. № 6. S. 453-462.
  19. Shpakov A.O., Shpakova E.A., Tarasenko I.I. et al. The peptides mimicking the third intracellular loop of 5-hydroxytryptamine receptors of the types 1B and 6 selectively activate G proteins and receptor-specifically inhibit serotonin signaling via the adenylyl cyclase system // Int. J. Pept. Res. Ther. 2010. V. 16. P. 95-105.
  20. Hashim S., Liu Y.Y., Wang R., Anand-Srivastava M.B. Streptozotocin-induced diabetes impairs G-protein linked signal transduction in vascular smooth muscle // Mol. Cell. Biochem. 2002. V. 240. P. 57-65.
  21. Hashim S., Li Y., Nagakura A. et al. Modulation of G-protein expression and adenylyl cyclase signa­ling by high glucose in vascular smooth muscle // Cardiovasc. Res. 2004. V. 63. P. 709-718.
  22. Li Y., Descorbeth M., Anand-Srivastava M.B. Role of oxidative stress in high glucose-induced decreased expression of Gialpha proteins and adenylyl cyclase signaling in vascular smooth muscle cells // Am. J. Physiol. 2008. V. 294. P. 2845-2854.
  23. Descorbeth M., Anand-Srivastava M.B. Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells // Free Radic. Biol. Med. 2010. V. 49. P. 1395-1405.
  24. Matsuda N., Hattori Y., Gando S. et al. Diabetes-induced down-regulation of β1-AR mRNA expression in rat heart // Biochem. Pharmacol. 1999. V. 58. P. 881-885.
  25. Michel A., Cros G.H., McNeill J.H., Serrano J.J. Cardiac adenylate cyclase activity in streptozotocin-treated rats after 4 months of diabetes: impairment of epinephrine and glucagon stimulation // Life Sci. 1985. V. 37. P. 2067-2075.
  26. Wichelhaus A., Russ M., Petersen S., Eckel J. G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats // Am. J. Physiol. 1994. V. 267. P. 548-555.
  27. Bruno J., Xu Y., Song J., Berelowitz M. Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat // Endocrinology. 1994. V. 135. P. 1787-1792.
  28. Carmena M.J., Clemente C., Carrero I. et al. G-proteins and beta-adrenergic stimulation of adenylate cyclase activity in the diabetic rat prostate // Prostate. 1997. V. 33. P. 46-54.
  29. Rodriguez-Pena M.S., Guijarro L.G., Juarranz M.G. et al. Analysis of vasoactive intestinal peptide receptors and the G protein regulation of adenylyl cyclase in seminal vesicle membranes from streptozotocin-diabetic rats // Cell. Signal. 1994. V. 6. P. 147-156.