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Effects of the start time of glycemic control on erectile function in streptozotocin-induced diabetic rats

Abstract

Diabetes-induced ED correlates with diabetes duration and glycemic control. This study evaluated the effect of glycemic control start time on erectile function in streptozotocin-induced diabetic rats. Rats were divided into normal controls (C); untreated diabetic rats (DM); and rats treated after 7 weeks (7W), and 10 weeks (10W) from DM. Treated diabetic rats received a timed daily injection of insulin. After 14 weeks of lab-controlled diabetes, experiments were performed. Group DM showed the ratio of intracavernosal pressure, significantly lower than other groups (10W vs DM; P<0.001). Groups 7W and 10W responded similarly, but did not recover to normal level (group C vs 7W; P<0.001). The percentage of α-smooth muscle actin increased more with earlier start times, and group DM’s percentages decreased significantly (group 10W vs DM; P<0.001). Apoptosis recovered significantly only in group 7W, comparable to group C. As start times became earlier, for all molecules (eNOS, Akt, MYPT1 and PECAM-1), treatment groups’ results neared those of group C. In conclusion, erectile function of diabetic rats recovered closer to normal controls if diabetic treatment started earlier. And the level of glycemic control was expected to be more important than the start time of diabetic treatment.

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References

  1. 1

    Althof SE, Buvat J, Gutkin SW, Belger M, Stothard DR, Fugl-Meyer AR . Sexual satisfaction in men with erectile dysfunction: correlates and potential predictors. J Sex Med 2010; 7: 203–215.

    Article  Google Scholar 

  2. 2

    Cho SY, Park K, Paick JS, Kim SW . Change of erectile function and responsiveness to phosphodiesterase type 5 inhibitors at different stages of streptozotocin-induced diabetes in rats. J Sex Med 2011; 8: 1352–1361.

    CAS  Article  Google Scholar 

  3. 3

    Cho SY, Chai JS, Lee SH, Park K, Paick JS, Kim SW . Investigation of the effects of the level of glycemic control on erectile function and pathophysiological mechanisms in diabetic rats. J Sex Med 2012; 9: 1550–1558.

    CAS  Article  Google Scholar 

  4. 4

    Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61.

    CAS  Article  Google Scholar 

  5. 5

    Sáenz de Tejada I, Angulo J, Cellek S, González-Cadavid N, Heaton J, Pickard R et al. Pathophysiology of erectile dysfunction. J Sex Med 2005; 2: 26–39.

    Article  Google Scholar 

  6. 6

    Costabile RA . Optimizing treatment for diabetes mellitus induced erectile dysfunction. J Urol 2003; 170: S35–S38.

    Article  Google Scholar 

  7. 7

    Sopko NA, Hannan JL, Bivalacqua TJ . Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nat Rev Urol 2014; 11: 622–628.

    CAS  Article  Google Scholar 

  8. 8

    Romeo JH, Seftel AD, Madhun ZT, Aron DC . Sexual function in men with diabetes type 2: association with glycemic control. J Urol 2000; 163: 788–791.

    CAS  Article  Google Scholar 

  9. 9

    Cellek S, Foxwell NA, Moncada S . Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats. Diabetes 2003; 52: 2353–2362.

    CAS  Article  Google Scholar 

  10. 10

    Park K, Ryu KS, Li WJ, Kim SW, Paick JS . Chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction. Eur Urol 2008; 53: 1282–1288.

    CAS  Article  Google Scholar 

  11. 11

    Li WJ, Park K, Paick JS, Kim SW . Chronic treatment with an oral rho-kinase inhibitor restores erectile function by suppressing corporal apoptosis in diabetic rats. J Sex Med 2011; 8: 400–410.

    CAS  Article  Google Scholar 

  12. 12

    Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB . Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol 2000; 163: 460–463.

    CAS  Article  Google Scholar 

  13. 13

    Bacon CG, Hu FB, Giovannucci E, Glasser DB, Mittleman MA, Rimm EB . Association of type and duration of diabetes with erectile dysfunction in a large cohort of men. Diabetes Care 2002; 25: 1458–1463.

    Article  Google Scholar 

  14. 14

    Fedele D, Coscelli C, Santeusanio F, Bortolotti A, Chatenoud L, Colli E et al. Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici. Diabetes Care 1998; 21: 1973–1977.

    CAS  Article  Google Scholar 

  15. 15

    Greene DA, Lattimer S, Ulbrecht J, Carroll P . Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 1985; 8: 290–299.

    CAS  Article  Google Scholar 

  16. 16

    Thompson EW . Structural manifestations of cardiomyopathy in the rat and its reversal by insulin treatment. Am J Anat 1988; 182: 270–282.

    CAS  Article  Google Scholar 

  17. 17

    Kern TS, Engerman RL . Arrest of glomerulopathy in diabetic dogs by improved glycemic control. Diabetologia 1990; 33: 522–525.

    CAS  Article  Google Scholar 

  18. 18

    Park K, Cho SY, Kim SW . Erectile response to type 5 phosphodiesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetes. Int J Androl 2011; 34: e468–e474.

    CAS  Article  Google Scholar 

  19. 19

    Yang J, Wang T, Yang J, Rao K, Zhan Y, Chen RB et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology 2013; 1: 487–494.

    CAS  Article  Google Scholar 

  20. 20

    Wang L, Tian W, Uwais Z, Li G, Li H, Guan R et al. AGE-breaker ALT-711 plus insulin could restore erectile function in streptozocin-induced type 1 diabetic rats. J Sex Med 2014; 11: 1452–1462.

    CAS  Article  Google Scholar 

  21. 21

    Van Den Eeden SK, Sarma AV, Rutledge BN, Cleary PA, Kusek JW, Nyberg LM et al. Effect of intensive glycemic control and diabetes complications on lower urinary tract symptoms in men with type 1 diabetes: Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabetes Care 2009; 32: 664–670.

    Article  Google Scholar 

  22. 22

    Awad H, Salem A, Gadalla A, El Wafa NA, Mohamed OA . Erectile function in men with diabetes type 2: correlation with glycemic control. Int J Impot Res 2010; 22: 36–39.

    CAS  Article  Google Scholar 

  23. 23

    Jensen VF, Bøgh IB, Lykkesfeldt J . Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies. J Neuroendocrinol 2014; 26: 123–150.

    CAS  Article  Google Scholar 

  24. 24

    IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med 2006; 23: 579–593.

    Article  Google Scholar 

  25. 25

    American Diabetes Association. Standards of medical care in diabetes—2007. Diabetes Care 2007; 30: S4–S41.

    Article  Google Scholar 

  26. 26

    Authors/Task Force Members Authors/Task Force Members Rydén L Authors/Task Force Members Grant PJ Authors/Task Force Members Anker SD Authors/Task Force Members Berne C Authors/Task Force Members Cosentino F et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34: 3035–3087.

    Article  Google Scholar 

  27. 27

    Jin HR, Chung YG, Kim WJ, Zhang LW, Piao S, Tuvshintur B et al. A mouse model of cavernous nerve injury–induced erectile dysfunction: functional and morphological characterization of the corpus cavernosum. J Sex Med 2010; 7: 3351–3364.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by grant no.03-2013-014-0 from the SNUH Research Fund.

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Correspondence to S W Kim.

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Kwon, O., Cho, S., Paick, JS. et al. Effects of the start time of glycemic control on erectile function in streptozotocin-induced diabetic rats. Int J Impot Res 29, 23–29 (2017). https://doi.org/10.1038/ijir.2016.39

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