AbstractMeasurement of consumed water and daily diuresis proved the pathomorphological manifestations of streptozotocin-induced cystopathy in the experiment on rats according to the results of biochemical studies of blood and urine. It is argued that the desquamation of cells in the transitional epithelium, its atrophy, stratification violation, and baring of the basal membrane are caused by a large volume of urine, which excessively stretches the urinary bladder, destroying the intercellular contacts of the urothelial layer. It is proved that primary hyperglycemia leads to widening of the lumen of the arterioles and moderate thickening of the basal membrane of the micro-hemovessels, and high chronic hyperglycemia – directly triggers the whole cascade of pathomorphological changes: on the 42nd day of the experiment it causes vasoconstriction of the arterioles, and at the later terms – the secondary expansion of the arterioles and venules of the microcirculatory bed of UB (urinary bladder); is the cause of dystrophic changes of endothelial cells, further thickening and lamellar transformation of the basal membrane and plasma permeation of the perivascular connective tissue; causes the appearance of dark involutional myocytes with few organelles and sarcoplasm sequestration. Hydropic dystrophy of smooth myocytes has been found to be associated with the hydration of blood plasma as a result of excessive polydipsia in diabetic animals, and vacuole dystrophy of urothelial cells, enlargement of their size and interstitial edema – with low specific urinary density due to the multiple fast increase of diuresis. It has been established that prolonged high glucosuria and decreased diuresis lead to a decrease in urothelial cell size, compaction of their cytoplasm and ultrastructural readjustment. The increase of the content of glycosylated hemoglobin during the experiment justified the appearance and increase of the sludge-syndrome.
Blyshchak NB. Structural restructuring of the submandibular salivary glands of the rat and their vascular bed under experimental diabetes mellitus. Visnyk morfolohiyi. 2014; 20 (1): 129-132.
Boleyeva HS. Regulatory changes in kidney arteries in rats in type I diabetes mellitus: author. diss. for candidate of biol. sciences: specialty 03.03.01 "Fiziologiya". 2013; 24.
Hanonh VF. Human physiology: a textbook. Lviv: Bak. 2002; 784.
Holovatskyy AS. Microstructural skin changes in experimental diabetes mellitus. Visnyk Ukrayinskoyi medychnoyi stomatolohichnoyi akademiyi. 2015; 15 (4): 220-223.
Korolev VA. Diagnosis of hyperglycemia in the clinic. Laboratornaya diagnostika. 2010; 54 (4): 10-21.
Krutikov ES. Changes in capillaroscopy in patients with type I diabetes mellitus in the development of chronic complications. Mezhdunarodnyy endokrinologicheskiy zhurnal. 2014; 2 (58): 40-44.
Kuzmin IV, Shabudina NO. Pathogenetic basis for the development of diabetic cystopathy. Experimental and clinical urology. 2014; 4: 92-98.
Paltov YeV, Kryvko YuYa, Fik VB, et al. Morphofunctional changes of vascular walls of the hemomicrocirculatory bed against a background of diabetic parodontopathies (literature review). Eksperymentalna ta klinichna fiziolohiya i biokhimiya. 2008; 42 (2): 81-86.
Nepomniashchikh LM, Lushnikova LYe, Neymark AI. Remodeling of the muscular membrane (detrusor) of a hyperactive urinary bladder in prostatic hyperplasia. Byulleten eksperimentalnoy biologii i meditsiny. 2012; 153 (5): 742-747. DOI: https://doi.org/10.1007/s10517-012-1825-2 [PMid:23113284]
Rozhivanov RV, Akimova AN, Dubsky SA, et al. Peculiarities of diseases of the genitourinary system in diabetes mellitus. Diagnostika, kontrol i lecheniye. 2009; 2: 40-45. DOI: https://doi.org/10.14341/2072-0351-5396
Pokotylo PB. Angioarchitectonics of rat kidney normally and experimental diabetes mellitus: auth. diss. for the scientif. degree of Candidate of med. sciences: specialty 14.03.01 "Normal Anatomy". Lviv: 2013; 19.
Nepomniashchikh LM, Lushnikova LYe, Neymark AI, et al. The role of structural-functional changes in the smooth muscle cells of the detrusor and prostate gland in the development of hyperactive urinary bladder. Fundamentalnyye issledovaniya. 2012; 5: 68-73.
Savka II. Morphology of the rat egg and its vascular bed normally and in streptozotocin-induced -induced diabetes mellitus: auth. diss. for the scientif. degree of cand. of med. sciences: specialty 14.03.01 "Normal Anatomy". Lviv: 2014; 20.
Shlopov VH. Pathological anatomy: textbook. Vinnytsia: Nova Knyha. 2004; 768.
Yarek-Martynova IR, Shestakova MV. Diabetes mellitus and endothelial dysfunction. Sakharnyy diabet. 2004; 2: 48-52. DOI: https://doi.org/10.14341/2072-0351-5609
Alberti KG, Zimmet P. Global burden of disease-where does diabetes mellitus fit in? Nat Rev Endocrinol. 2013; 9(5): 258-260. DOI: https://doi.org/10.1038/nrendo.2013.54 [PMid:23478328]
Yonekubo S, Tatemichi S, Maruyama K, Kobayashi M. Alpha1A-adrenoceptor antagonist improves underactive bladder associated with diabetic cystopathy via bladder blood flow in rats. BMC Urology. 2017; 17: 64-72. DOI: https://doi.org/10.1186/s12894-017-0256-9 [PMid:28835278 PMCid:PMC5569480]
American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015; 38(1): 8-16. DOI: https://doi.org/10.2337/dc15-S005 [PMid:25537714]
Atalik KE. Diabetes mellitus- and cooling-induced bladder contraction: an in vitro study. J Smooth Mus Res. 2010; 46(4): 175183. DOI: https://doi.org/10.1540/jsmr.46.175 [PMid:20859065]
Birder LA, Andersson KE. Urothelial signaling. Physiol Rev. 2013; 93: 653-680. DOI: https://doi.org/10.1152/physrev.00030.2012 [PMid:23589830 PMCid:PMC3768101]
Choi H, Bae1 JH, Oh CY, et al. Clinical Efficacy of Solifenacin in the Management of Diabetes Mellitus-Associated Versus Idiopathic Overactive Bladder Symptoms: A Multicenter Prospective Study. Int Neurourol J. 2018; 22; 51-57. DOI: https://doi.org/10.5213/inj.1834982.491 [PMid:29609421 PMCid:PMC5885131]
Oikawa J, Ukawa S, Ohira H, et al. Diabetes mellitus is associated with low secretion rates of immunoglobulin in saliva. J Epidemiol. 2015; 25(7): 470-474. DOI: https://doi.org/10.2188/jea.JE20140088 [PMid:26094794 PMCid:PMC4483372]
Wittig L, Carlson KV, Andrews JM, et al. Diabetic bladder dysfunction: a review. Urology. 2019; 123:1-6. DOI: https://doi.org/10.1016/j.urology.2018.10.010 [PMid:30352207]
Inouye BM, Hughes FM, Jin H, et al. Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria. Research and Reports in Urology. 2018; 10: 219-225. DOI: https://doi.org/10.2147/RRU.S177633 [PMid:30533402 PMCid:PMC6247963]
Ellenbroek JH, Inan EA, Mitchel MC. A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences. Neurourology and Urodynamics. 2018; 37: 2346-2360. DOI: https://doi.org/10.1002/nau.23786 [PMid:30152546]
Spector DA, Wade JB, Dillow R, et al. Expression, localization, and regulation of aquaporin-1 to -3 in rat urothelia. Am J Physiol Renal Physiol. 2002; 282:1034 - 1042. DOI: https://doi.org/10.1152/ajprenal.00136.2001 [PMid:11997319]
Hill SR, Fayyard SR, Jones GR. Diabetes mellitus and female lower urinary tract symptoms: a review. Neurourol Urodynam. 2008; 27:362-368. DOI: https://doi.org/10.1002/nau.20533 [PMid:18041770]
Hanna-Mitchell AT, Ruiz GW, Danechgari F, et al. Impact of diabetes mellitus on bladder uroepithelial cells. Am J Physiol Regul Integr Comp Physiol. 2013; 304(2): 84-93. DOI: https://doi.org/10.1152/ajpregu.00129.2012 [PMid:23174855 PMCid:PMC3543662]
Inan EA, Ellenbroek JH, Michel MC. A systematic review of urinary bladder hypertrophy in experimental diabetes: Part I. Streptozotocin-induced -induced rat models. Neurourology and Urodynamics. 2018; 37:1212-1219. DOI: https://doi.org/10.1002/nau.23490 [PMid:29392751]
International Diabetes Federation. IDF diabetes atlas. Brussels: International Diabetes Federation. 2015; 144.
Khandelwal P, Abraham SN, Apodaca G. Cell biology and physiology of the uroepithelium. Am J Physiol Renal Physiol. 2009; 297(6):1477-1501. DOI: https://doi.org/10.1152/ajprenal.00327.2009 [PMid:19587142 PMCid:PMC2801337]
Liu G, Daneshgari F. Temporal diabetes- and diuresis-induced remodeling of the urinary bladder in the rat. Am J Physiol Regul Integ Comp Physiol. 2006; 291: 837-843. DOI: https://doi.org/10.1152/ajpregu.00917.2005 [PMid:16513765]
Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 27 million participants. Lancet. 2011; 378(9785): 31-40. DOI: https://doi.org/10.1016/S0140-6736(11)60679-X
Li WJ, Xu M, Gu M, et al. Poly(ADP-ribose) polymerase inhibition restores bladder function by suppressing bladder apoptosis in diabetic rats. Int J Clin Exp Pathol. 2017;10(4): 4451-4460.
Srivastava PK, Srivastava S, Singh AK, et al. Role of ayurveda in management of diabetes mellitus. Inter Res J Pharm. 2015; 6(1): 8-9. DOI: https://doi.org/10.7897/2230-8407.0613
Spector DA, Yang Q, Wade JB. High urea and creatinine concentrations and urea transporter in mammalian urinary tract tissues. Am J Physiol Renal Physiol. 2007; 292(1): 467-474. DOI: https://doi.org/10.1152/ajprenal.00181.2006 [PMid:16849692]
Yang S, Wang D, Cao X, et al. Store operated calcium channels are associated with diabetic cystopathy in streptozotocin-induced induced diabetic rats. Molecular Medicine Reports. 2018; 17: 6612-6620. DOI: https://doi.org/10.3892/mmr.2018.8723 [PMid:29532875 PMCid:PMC5928646]
Han JS, Min YS, Kim GH, et al. The change of signaling pathway on the electrical stimulated contraction in streptozotocin-induced -induced bladder dysfunction of rats. Korean J Physiol Pharmacol. 2018; 22(5): 577-584. DOI: https://doi.org/10.4196/kjpp.2018.22.5.577 [PMid:30181704 PMCid:PMC6115354]
He P, Zhou XZ, Shen WH, et al. The function of hyperpolarization-activated cyclic nucleotide-gated channel in diabetic cystopathy. European Review for Medical and Pharmacological Sciences. 2018; 22: 6575-6582.
Han JS, Kim SJ, Nam Y, et al. The Inhibitory Mechanism on Acetylcholine-Induced Contraction of Bladder Smooth Muscle in the Streptozotocin-induced -Induced Diabetic Rat. Biomol Ther. 2019; 27(1):101-106. DOI: https://doi.org/10.4062/biomolther.2018.136 [PMid:30419634 PMCid:PMC6319557]
Lee SE, Ma W, Rattigan EM, et al. Ultrastructural features of retinal capillary basement membrane thickening in diabetic swine. Ultrastruct Pathol. 2010; 34(1): 35-41. DOI: https://doi.org/10.3109/01913120903308583 [PMid:20070152 PMCid:PMC3085508]
Klee NS, McCarthy CG, Lewis S, et al. Urothelial Senescence in the Pathophysiology of Diabetic Bladder Dysfunction - A Novel Hypothesis. Hypothesis and Theory. 2018; 5. DOI: https://doi.org/10.3389/fsurg.2018.00072 [PMid:30564582 PMCid:PMC6288180]
Vojtková J, Čiljaková M, Bánovčin P. Diabetic microangiopathy - etiopathogenesis, new possibilities in diagnostics and management. Microangiopathy. InTech. 2012; 37- 66. DOI: https://doi.org/10.5772/31103
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews Endocrinology. 2017. DOI: https://doi.org/10.1038/nrendo.2017.151 [PMid:29219149]
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