2.Diabetic bladder dysfunction.
Guiming LIU ; Firouz DANESHGARI
Chinese Medical Journal 2014;127(7):1357-1364
OBJECTIVETo review studies on diabetic bladder dysfunction (DBD), a common and bothersome complication of diabetes mellitus.
DATA SOURCESWe performed a search of the English literature through PubMed. The key words used were "diabetes" and "bladder dysfunction" or "cystopathy". Our own data and perspective are included in the discussion.
STUDY SELECTIONStudies containing data relevant to DBD were selected. Because of the limited length of this article, we also referenced reviews that contain comprehensive amalgamations of relevant literature.
RESULTSThe classic symptoms of DBD are decreased bladder sensation, increased bladder capacity, and impaired bladder emptying with resultant elevated post-void residual urine. However, recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes. Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes, causing an early phase of compensatory bladder function and a later phase of decompensated bladder function. The pathophysiology of DBD is multifactorial, including disturbances of the detrusor, urothelium, autonomic nerves, and urethra. Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes. Polyuria causes significant bladder hypertrophy in the early stage of diabetes, whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.
CONCLUSIONSDBD includes time-dependent and mixed manifestations. The pathological alterations include muscle, nerve, and urothelium. Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD. Treatments for DBD are limited. Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately. Animal studies of DBD in type 2 diabetes are needed, from the natural history to mechanisms. Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.
Animals ; Diabetes Mellitus, Experimental ; complications ; Humans ; Urinary Bladder Diseases ; diagnosis ; physiopathology
4.Establishment and evaluation of a rat model of type 2 diabetes associated with depression.
Na LI ; Qun LIU ; Xiao-juan LI ; Xiao-hui BAI ; Yue-yun LIU ; Zhong-ye JIN ; Yu-xia JING ; Zhi-yi YAN ; Jia-xu CHEN
Chinese Journal of Applied Physiology 2015;31(1):23-26
OBJECTIVETo establish and evaluate a rat model of type 2 diabetes mellitus (T2DM) associated with depression for further elaborating the disease.
METHODSTwenty-four Wistar rats were randomly divided into three groups: normal group (group N), T2DM group (group T) and T2DM with depression group (group T + D), with 8 rats in each group. The T2DM rat model was induced by high fat diet and low dose of Streptozotocin (STZ) injection, and in addition, the T2DM rats were made restraint stress for 21 days. After the model was established, the insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed. Then the rat depression level was analyzed by open field test, and the concentration of 5-hydroxytryptamine (5-HT) and dopamine (DA)was determined by ELISA to confirm the model identity.
RESULTSThe blood glucose level in group T and group T + D didn't return to the normal level at 180 minutes in the ITT and OGTT test; Compared with the group N, the max movement distance, retaining time in the central zone and the retaining frequency within 5 minutes in the group T + D decreased; 5-HT and DA level in the serum of rats in. group T + D was reduced.
CONCLUSIONA rat model of type 2 diabetes mellitus associated with depression has been successfully established by high fat diet and injection of low dose streptozotocin in combination with restraint stress for 21 days. This rat model is useful for further relevant studies.
Animals ; Depression ; complications ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; Diet, High-Fat ; Glucose Tolerance Test ; Rats ; Rats, Wistar ; Restraint, Physical ; Serotonin ; Streptozocin ; Stress, Psychological
5.Mechanisms of hyperkalemia associated with hyporeninemic hypoaldosteronism in streptozotocin-induced diabetic rats.
Journal of Korean Medical Science 1994;9(2):107-115
This study was aimed at investigating the mechanisms of clinically important overt hyperkalemia in diabetes mellitus with underlying hyporeninemic hypoaldosteronism known as a classic model of the syndrome of hyporeninemic hypoaldosteronism (SHH). Rats (Sprague-Dawley, male) were streptozotocin-treated (60 mg/kg, ip) and used after 60 days. Rats with plasma glucose levels higher than 300 mg/dL (mean +/- SEM, 423 +/- 20 mg/dL, n = 8) were selected as the diabetic group. Age-matched normal rats served as control (mean plasma glucose, 88 +/- 2, mg/dL, n = 8). Serum potassium concentrations and osmolalities as well as serum creatinine levels were significantly higher in the diabetic than in the control group (5.07 +/- 0.09 vs. 4.68 +/- 0.11 mEq/L; 330 +/- 14 vs 290 +/- 3 mOsm/L; 0.40 +/- 0.03 vs 0.31 +/- 0.02 mg/dL, p < 0.05). Plasma renin activity (PRA) in the diabetic group was significantly lower than that in the control group (6.0 +/- 1.0 vs 12.1 +/- 1.1 ng Al/ml/h, p < 0.001). Plasma aldosterone concentration (PAC) was also significantly lower in the former than in the latter (368 +/- 30 vs 761 +/- 57 pg/ml, p < 0.001). Renomegaly, abnormal distal tubular cells with few organelles, and increased lipid droplets with pyknotic nucleus in zona glomerulosa of the adrenal glands were noted in the diabetic group. In conclusion, multifactorial causes including insulinopenia, hyperosmolality, elevated serum creatinine level and hypoaldosteronism with possible contribution of altered distal tubular response to aldosterone may have interacted to develop hyperkalemia in these diabetic rats.
Animals
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Diabetes Mellitus, Experimental/blood/*complications/pathology
;
Disease Models, Animal
;
Hyperkalemia/*complications
;
Hypoaldosteronism/*complications
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Kidney Tubules, Distal/ultrastructure
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Male
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Rats
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Rats, Sprague-Dawley
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Reference Values
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Zona Glomerulosa/ultrastructure
6.Mechanisms of impaired perfusion recovery in type 1 diabetic mouse.
Yong-Jun LI ; Xia-Lin LLU ; Chang-Wei LIU ; Heng GUAN ; Qing LIN
Acta Academiae Medicinae Sinicae 2007;29(6):742-746
OBJECTIVETo investigate the perfusion restoration of type 1 diabetic mouse under the setting of surgically induced hind limb ischemia and the number and function of bone marrow endothelial progenitor cells (EPCs).
METHODSForty mice were randomly divided into two groups: one group was injected with alloxan through tail vein to induce type 1 diabetes mellitus, and another group was set as control group. All mice were surgically induced to hind limb ischemia. Blood flow was monitored with Laser Doppler perfusion imaging for 4 weeks after artery ligation. Ten mice in each group were sacrificed and muscle tissues were harvested for histological detection. The remaining mice were sacrificed 7 days after surgery, bone marrow mesenchymal stem cells were harvested and EPCs were analyzed by flow cytometry and then were collected to culture for functional detection.
RESULTSAll mice received alloxan injection showed typical symptoms of type 1 diabetes mellitus. Restoration of blood flow was significantly slower in type 1 diabetic mice with lower level of vascular density in ischemic muscles than control group (P < 0.001, P < 0.05). The number and function of EPCs (CD34 and vascular endothelial growth factor receptor 2 double positive cells) in type 1 diabetic mice were significantly lower than that in control mice (P < 0.05).
CONCLUSIONSThe spontaneous angiogenesis is attenuated with a decreased number and function of EPCs in the setting of type 1 diabetes mellitus. This may partly explain why diabetic patients with peripheral artery diseases have more aggressive disease and poorer outcome.
Animals ; Antigens, CD34 ; analysis ; Cell Count ; Diabetes Mellitus, Experimental ; complications ; pathology ; Diabetes Mellitus, Type 1 ; complications ; Hindlimb ; blood supply ; Ischemia ; complications ; physiopathology ; Mesenchymal Stromal Cells ; chemistry ; Mice ; Reperfusion ; Vascular Endothelial Growth Factor Receptor-2 ; analysis
7.Association of dendritic cell distribution with intima hyperplasia in rats with diabetes mellitus.
Qiang FU ; Zhi-liang LI ; Xiao-hua FU ; Xiao LEI ; Fei MIAO ; Hong-chao WU ; Ying-feng LIU
Journal of Southern Medical University 2008;28(2):196-199
OBJECTIVETo investigate the association of dendritic cell distribution in the peripheral blood, spleen and arterial wall with intimal hyperplasia in rats with diabetes mellitus.
METHODSDiabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin and high-fat feeding for 8 weeks. Peripheral blood, arterial wall and the spleen were collected from the rats to prepare cell suspensions, in which the proportions of dendritic cells and T cells were determined by flow cytometry.
RESULTSThe tunica intimal hyperplasia was more obvious in diabetic rats with or without high-fat feeding as compared with that of the control rats (P<0.05), and their dendritic cells decreased significantly in the peripheral blood (P<0.05) but increased in the arterial wall. The percentage of T cells was also increased in the peripheral blood and arterial wall of the diabetic rats.
CONCLUSIONChanges in the distribution of dendritic cells and T cells are closely associated with intimal hyperplasia in diabetic rats, suggesting the involvement of dendritic cells and T cells in the formation of atherosclerosis.
Animals ; Dendritic Cells ; cytology ; Diabetes Mellitus, Experimental ; complications ; pathology ; Hyperplasia ; complications ; pathology ; Rats ; Rats, Sprague-Dawley ; Spleen ; cytology ; Streptozocin ; T-Lymphocytes ; cytology ; Tunica Intima ; pathology
8.Influence of advanced glycosylation end products on wound healing of burn rats with diabetes.
Kui GE ; Yi-wen NIU ; Ting XIE ; Wei-dong LIN ; Ming TIAN ; Bing XU ; Shi-tao CUI ; Shu-liang LU
Chinese Journal of Burns 2009;25(6):433-436
OBJECTIVETo understand the influence of accumulation of advanced glycosylation end products (AGE) on wound healing of burn rats complicated with diabetes.
METHODSSeventy-five SD rats were divided into control, diabetes, and aminoguanidine-interfered groups in completely randomized method, with 25 rats in each group. All rats were subjected to deep partial-thickness scald. Diabetes was reproduced in rats of diabetes and aminoguanidine-interfered groups. Rats in aminoguanidine-interfered group were fed with 100 mg x kg(-1) xd (-1) aminoguanidine. Rats were sacrificed on post-scald day (PSD) 0, 3, 7, 14, and 21, and portrait of the wounds were taken. Full-thickness skin tissue specimens were obtained for determination. Specimens of epidermis from back of SD rats were obtained for KC cultivation and verification. Wound healing rate, glucose content in skin tissue, morphologic change in wound tissue, AGE distribution in skin tissue, influence of AGE on proliferation and apoptosis of KC were observed.
RESULTSWound healing rate of rats was respectively lower in diabetes group than that in control group on PSD 7, 14, and 21 (P < 0.01), but it was obviously higher in aminoguanidine-interfered group than that in the former 2 groups (P < 0.01). Glucose content of rat skin in diabetes group was (2.62 +/- 0.19) mmol/g, and it was (2.58 +/- 0.07) mmol/g in aminoguanidine-interfered group, both higher than that in control group [(1.04 +/- 0.09) mmol/g, P < 0.01]. In control group, limited intensive infiltration of inflammatory cells was found in the wound with necrotic tissue formation which fell off in time, and with no obvious delay of wound healing. In diabetes group, infiltration of inflammatory cells in wounds of rats appeared slowly, but diffusely and persistently; necrotic tissue formed and fell off late in time, with obvious delay of wound healing. In aminoguanidine-interfered group, intensive infiltration of inflammatory cells was observed in time, and the time of necrotic tissue formation and sloughing, and wound healing were respectively earlier than that in diabetes group. Sporadic disposition of small amount of AGE was found in rats in control group. AGE accumulation increased significantly in rats in diabetes group. AGE content decreased significantly in rats in aminoguanidine-interfered group after administration of aminoguanidine. KC proliferation decreased significantly in concentration dependent manner 48 hours after AGE stimulation. Absorbance value of AGE decreased in each AGE-interfered group (P < 0.01). Early Annexin-V positive apoptotic KC rate was obviously higher in 100 ug/mL AGE-interfered group (15.1 +/- 2.3)% than that in control group [(11.2 +/- 1.2)%, P < 0.05]. There was no statistical significance between 100 ug/mL AGE-interfered group (14.3 +/- 3.5)% and control group (15.2 +/- 2.4)% in respect of the rate of double-positive cells apoptosis at final stage (P > 0.05).
CONCLUSIONSHyperglycemia may inhibit proliferation of repairing cells such as KC through AGE accumulation, thus impedes wound healing. Reduction of AGE accumulation could ameliorate wound healing delay due to diabetes.
Animals ; Blood Glucose ; metabolism ; Burns ; complications ; metabolism ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Glycation End Products, Advanced ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Wound Healing
9.The Role of Free Radical in the Pathogenesis of Impotence in Streptozotocin-Induced Diabetic Rats.
Ji Kan RYU ; Dae Joong KIM ; Taek LEE ; Yun Seog KANG ; Sang Min YOON ; Jun Kyu SUH
Yonsei Medical Journal 2003;44(2):236-241
Diabetes is the most common cause of erectile dysfunction (ED). Oxidative stress has been suggested to be a contributory factor in vascular complications of diabetes in various organs. In the present study, we investigated whether oxidative stress is associated with erectile function in non- insulin dependant diabetes mellitus (NIDDM) rats. Fifty-four Sprague-Dawley rats were the subjects of this study. In each rat, NIDDM was induced by an intraperitoneal injection of 90mg/Kg of streptozotocin on the second day after birth. Based on the diabetic period, they were classified into either short-term or long-term diabetics (avg. 22 weeks, n=18 and avg. 38 weeks, n=20), respectively, and their age-matched controls (n=16). To evaluate the erectile function in each rat, the intracavernous pressure, and latency to maximal pressure, following cavernous nerve stimulation (frequency: 1 Hz, intensity: 3 - 6 V, pulse width: 1 msec, pulse duration: 1 min.) was analyzed. To evaluate both oxidative stress from reactive oxygen species, and antioxidant function as a defense against them, total malondialdehyde and glutathione levels were measured in the corpus cavernosum of the penis, using a spectrophotometric assay. The intracavernous pressure following cavernous nerve stimulation was significantly lower in the long-term (49.8 +/- 9.4 cmH2O) than the short-term diabetics (75.9 +/- 14.8 cm H2O), and markedly decreased in the diabetic rats, compared with their age-matched controls (long-term controls; 60.7 +/- 17.2 cmH2O, short-term controls; 95.2 +/- 20.4 cmH2O). The malondialdehyde content in the corpus cavernosum was markedly increased in the diabetics (2.13 +/- 0.27 nM/mg protein) compared to the controls (1.48 +/- 0.22 nM/mg protein). Furthermore, the glutathione level was significantly decreased in the diabetics, compared to age-matched controls (short-term control; 218.3 +/- 25.6 microM/mg protein, long-term control; 150.2 +/- 9.8 microM/mg protein). In the diabetic groups, it was more significantly decreased in the long-term diabetics (134.8 +/- 11.3 microM/mg protein) than in short-term diabetics (182.1 +/- 18.8 microM/mg protein). NIDDM causes erectile dysfunction, which slowly progresses. Oxidative stress to cavernous tissue may be a contributory factor in erectile dysfunction in diabetics.
Animals
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Diabetes Mellitus, Experimental/*complications/metabolism
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Diabetes Mellitus, Type II/*complications
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Female
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*Free Radicals
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Glutathione/analysis
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Impotence/*etiology
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Lipid Peroxidation
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Male
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Rats
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Rats, Sprague-Dawley
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Streptozocin
;
Support, Non-U.S. Gov't
10.Non-canonical Wnt signaling contributes to development of non-alcoholic steatohepatitis in a rat model of type 2 diabetes mellitus.
Feng TIAN ; Ya-jie ZHANG ; Lin WANG
Chinese Journal of Hepatology 2013;21(7):537-542
OBJECTIVETo investigate the role of the non-canonical Wnt signaling pathway in development of non-alcoholic steatohepatitis (NASH) related to type 2 diabetes mellitus (T2DM) using a rat model.
METHODSTwenty-four male Sprague-Dawley rats were randomly divided into two equal groups: control group, fed a stand diet; T2DM-NASH model group, fed a high sucrose and fat diet for 4 weeks and intraperitoneally injected with streptozotocin (30 mg/kg). Twelve weeks after model establishment, all rats were sacrificed. Serum levels of glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by biochemical analysis. Liver pathological changes were assessed microscopically by hematoxylin-eosin and oil red O staining. The liver expression of Wnt5a and NF-kB p65 were detected by immunohistochemistry and western blotting (protein), and quantitative real-time PCR (mRNA).
RESULTSThe T2DM-NASH model group showed significantly higher levels of glucose (control group: 6.25 +/- 1.28 vs. 31.21 +/- 0.86 mmol/L, t = -36.204, P less than 0.01), ALT (31.00 +/- 3.69 vs. 301.50 +/- 8.62 U/L, t = -99.94, P less than 0.01), and AST (77.58 +/- 1.83 vs. 344.75 +/- 1.82 U/L, t = -358.85, P less than 0.01). The T2DM-NASH group also showed remarkable signs of steatosis and inflammation in hepatic tissues. The T2DM-NASH group had significantly higher integral optical density (IOD) detection of Wnt5a (control group: 1.15E4 +/- 577.45 vs. 4.04E5 +/- 2.42E4, t = -56.24, P less than 0.01) and NF-kB p65 (1.28E4 +/- 1.59E3 vs. 4.21E5 +/- 1.68E4, t = -83.895, P less than 0.01), as well as protein levels detected by western blot (Wnt5a: 4.21 +/- 0.34 vs. 1.00 +/- 0.25, t = 17.030, P less than 0.01; NF-kB p65: 4.93 +/- 0.76 vs. 1 +/- 0.13, t = 11.438, P less than 0.01). The hepatic mRNA levels followed the same trend (Wnt5a: 9.53 +/- 0.64 vs. 1.04 +/- 0.35, t = 20.165, P less than 0.01; NF-kB p65: 0.60 +/- 0.13 vs. 0.74 +/- 0.10, t = -1.802, P = 0.125). In the T2DM-NASH group, hepatic Wnt5a protein expression was positively correlated with ALT (r = 0.64, P less than 0.05), AST (r = 0.59, P less than 0.05), and NF-kB p65 protein expression (r = 0.58, P less than 0.05).
CONCLUSIONWnt5a may activate NF-kB to stimulate an inflammatory response leading to development of NASH related to T2DM.
Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Liver ; pathology ; Male ; Non-alcoholic Fatty Liver Disease ; etiology ; pathology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; Wnt-5a Protein