The effectiveness of insulin therapy in the functional and morphological recovery of leydig cells in rats submitted to Diabetes mellitus
Keywords:Diabetes Mellitus, Insulin Therapy, Leydig Cells, Seminiferous Tubule, Testis.
The effects of systemic insulin administration at different concentrations on the testicular tissue of diabetic adult rats, induced by streptozotocin, are evaluated by the morphological analysis of spermatogenic process. Twenty-four adult male rats were divided into 1) Control Group: they received citrate buffer, by intraperitoneal injection; 2) Diabetic Group: induced by intraperitoneal injection of streptozotocin (60 mg. kg-1 of body weight); 3) Insulin 50%: induced diabetes treated with half of standard dosage of insulin; 4) Insulin 100%: induced diabetes treated with standard dose of insulin. After eight weeks, animals were weighted and anesthetized; testicles were removed and processed in resin. Body and testicular weight of diabetic rats decreased when compared to that of control. Parameters increased with insulin therapy. Testosterone levels were low in diabetic animals but rates recovered after insulin therapy. Nuclear diameter and volume of Leydig cells decreased in diabetic rats although they significantly increased after insulin therapy. Results showed that the administration of insulin in diabetic rats promoted a protective effect of testicular parenchyma, enhancing efficient recovery on testosterone levels and increase in daily sperm production.
ABBASI, Z., et al. Effects of Sesame Oil on the Reproductive Parameters of Diabetes Mellitus-Induced Male Rats. The World Journal of Men’s Health. 2013, 31(2), 141 https://doi.org/10.5534/wjmh.2013.31.2.141
AMANN, R.P. and ALMQUIST, J.O. Reproductive Capacity of Dairy Bulls. VIII. Direct and Indirect Measurement of Testicular Sperm Production. Journal of Dairy Science. 1962, 45(6), 774–781. https://doi.org/10.3168/jds.S0022-0302(62)89487-9
BALLESTER, J., et al. Insulin-Dependent Diabetes Affects Testicular Function by FSH- and LH-Linked Mechanisms. Journal of Andrology. 2004, 25(5), 706–719. https://doi.org/10.1002/j.1939-4640.2004.tb02845.x
BALLESTER, J., et al. Tungstate treatment improves Leydig cell function in streptozotocin- diabetic rats. Journal of Andrology. 2005, 26(6), 706–715. https://doi.org/10.2164/jandrol.04156
BOONKUSOL, D., JUNSHUM, P. and PANPROMMIN, K. Gonadosomatic Index, Oocyte Development and Fecundity of the Snakehead Fish (Channa striata) in Natural River of Mae La, Singburi Province, Thailand. Pakistan Journal of Biological Science. 2020, 23(1), 1-8. https://doi.org/10.3923/pjbs.2020.1.8.
BRUNING, J.C., et al. Role of Brain Insulin Receptor in Control of Body Weight and Reproduction. Science, 2000, 289(5487), 2122-2125. https://doi.org/10.1126/science.289.5487.2122
CAMERON, D.F., MURRAY, F.T. and DRYLIE, D.D. Interstitial compartment pathology and spermatogenic disruption in testes from impotent diabetic men. The Anatomical Record. 1985, 213(1), 53–62. https://doi.org/10.1002/ar.1092130108
CONDORELLI, R.A., et al. Diabetes Mellitus and Infertility: Different Pathophysiological Effects in Type 1 and Type 2 on Sperm Function. Frontiers in Endocrinology (Lausanne). 2018, 9, 268. https://doi.org/10.3389/fendo.2018.00268
GOBBO, M.G., et al. Effect of Melatonin Intake on Oxidative Stress Biomarkers in Male Reproductive Organs of Rats under Experimental Diabetes. Oxidative Medicine and Cellular Longevity. 2015, 2015, 1-12. https://doi.org/10.1155/2015/614579
GOTO, T., et al. Testosterone Supplementation Rescues Spermatogenesis and In Vitro Fertilizing Ability of Sperm in Kiss1 Knockout Mice. Endocrinology. 2020, 161(9), bqaa092. https://doi.org/10.1210/endocr/bqaa092
GRIFFETH, R.J., CARRETERO, J. and BURKS, D.J. Insulin Receptor Substrate 2 Is Required for Testicular Development. PLoS ONE. 2013, 8(5), 119-129. https://doi.org/10.1371/journal.pone.0062103
GUO, Z., et al. Effect of Telmisartan or Insulin on the Expression of Adiponectin and its Receptors in the Testis of Streptozotocin-Induced Diabetic Rats. Hormone and Metabolic Research. 2016, 48(6), 404–412. https://doi.org/10.1055/s-0042-101549
HAJAM, Y.A. and RAI, S. Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats. Life Sciences. 2019, 239, 117046. https://doi.org/10.1016/j.lfs.2019.117046
HASSEN, N.S., ROUBI, N.M.E.I. and OMARA, E.A. Evaluation of the Influence of each of Melatonin and Chromium against Diabetes-Induced Alteration in the Testis of Albino Rats Using Light andElectron Microscopies. The Egyptian Journal of Hospital Medicine. 2007, 27(1), 143–162. https://doi.org/10.12816/ejhm.2007.17718
HE, Z., et al. Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms. In Vivo. 2021, 35(5), 2503-2511. https://doi.org/10.21873/invivo.12531
JOSHI, D., SARKAR, D. and SINGH, S. K. Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis. Biochemical and Biophysical Research Communications. 2017, 490(4), 1346–1354. https://doi.org/10.1016/j.bbrc.2017.07.026
KIANIFARD, D. The Histological, Histomorphometrical and Histochemical Changes of Testicular Tissue in the Metformin Treated and Untreated Streptozotocin-Induced Adult Diabetic Rats. Veterinary Research Forum. 2011, 2(1), 13–24.
LONG, L., et al. Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget. 2018, 9(4), 5321-5336. https://doi.org/10.18632/oncotarget.23915
MALLICK, C., et al. Protection of Testicular Dysfunctions by MTEC, a Formulated Herbal Drug, in Streptozotocin Induced Diabetic Rat. Biological & Pharmaceutical Bulletin. 2007, 30(1), 84–90. https://doi.org/10.1248/bpb.30.84
MARESCH, C. C., et al. Hyperglycemia is associated with reduced testicular function and activin dysregulation in the Ins2Akita+/− mouse model of type 1 diabetes. Molecular and Cellular Endocrinology. 2017, 446, 91–101. https://doi.org/10.1016/j.mce.2017.02.020
MARESCH, C.C., et al. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Human Reproductive Update. 2018, 24(1), 86-105. https://doi.org/10.1093/humupd/dmx033
MUNRO, C.J., et al. Relationship of serum estradiol and progesterone concentrations to the excretion profiles of their major urinary metabolites as measured by enzyme immunoassay and radioimmunoassay. Clinical Chemistry. 1991, 37(6), 838–844. https://doi.org/10.1093/clinchem/37.6.838
OLIVEIRA, J.S., et al. Histomorphometric and oxidative evaluation of the offspring's testis from type 2 diabetic female rats treated with metformin and pentoxifylline. International Journal of Experimental Pathology. 2022, 2022, 1-16. https://doi.org/10.1111/iep.12446
PEREIRA, A.S.B.F, et al. Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats. International Journal of Molecular Sciences. 2018, 19(11):3488. https://doi.org/10.3390/ijms19113488
PREECE, D.A., LITTLE, T.M. and HILLS, F.J. Agricultural Experimentation: Design and Analysis. Biometrics. 1982, 38(2), 524. https://doi.org/10.2307/2530470
RICCI, G., et al. Diabetic rat testes : morphological and functional alterations. Andrologia. 2009, 41(6), 361–368.
RODACKI, M., et al. Classificação do diabetes. Diretriz Oficial da Sociedade Brasileira de Diabetes (2022). https://doi.org/10.29327/557753.2022-1
SAMADIAN, Z., et al. Moderate-intensity exercise training ameliorates the diabetes-suppressed spermatogenesis and improves sperm parameters: Insole and simultaneous with insulin. Andrologia. 2019, 51(11), 1–11. https://doi.org/10.1111/and.13457
SANGUINETTI, R.E., et al. Ultrastructural Changes in Mouse Leydig Cells after Streptozotocin Administration. Experimental Animals. 1995, 44(1), 71-73. https://doi.org/10.1538/expanim.44.71
SCHOELLER, E.L., et al. Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary- gonadal axis in Akita diabetic mice and restores male fertility. Diabetes. 2012, 61(7), 1869–1878. https://doi.org/10.2337/db11-1527
SIMAN, V.A., et al. Spermatogenic dynamics of the spiny rat Kannabateomys amblyonyx (Wagner, 1845) (Rodentia, Echimyidae). Animal Reproduction Science. 2017, 184, 36-43.
TRINDADE, A.A.T., et al. Long term evaluation of morphometric and ultrastructural changes of testes of alloxan-induced diabetic rats. Acta Cirurgica Brasileira. 2013, 28(4), 256–265. https://doi.org/10.1590/S0102-86502013000400005
WAGNER, I.V., et al. Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible By Insulin Treatment. Endocrinology. 2021, 162(4), bqab017. https://doi.org/10.1210/endocr/bqab017
YARED, Z. and CHIASSON, J.L. Ketoacidosis and the hyperosmolar hyperglycemic state in adult diabetic patients: Diagnosis and treatment. Minerva Medica. 2003, 94(6), 409–418.
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Copyright (c) 2023 Alluanan Adelson do Nascimento Silva, Jessica Santana de Oliveira , Fernanda Carolina Ribeiro Dias , Rosana Nogueira de Moraes , Elizabeth Neves de Melo , Pierre Castro Soares , Valdemiro Amaro da Silva Júnior
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