In vitro electrical neurophysiological and behavioural studies have shown that diabetes mellitus negatively affects hippocampal function. In this study, by using in vivo extracellular recording, the spontaneous neural activity was obtained from hippocampus of anaesthetized rats in both streptozotocin-induced diabetes group and normal control group. Temporal relationship between neuronal firing and slow oscillation (1-4 Hz) of local field potentials (LFPs) in hippocampus was analyzed using coherence and phase locking measurement. Lower coherence value (0.617+/-0.028) was observed in diabetic rats than that in control rats (0.730+/-0.024) (P=0.005). Furthermore, phase-locking measurement using von Mises fitting parameterized by a concentration parameter kappa showed a lower degree (kappa= 0.347+/-0.113) of temporal coordination between neuronal spiking and slow oscillation of LFPs in the hippocampus of diabetic rats than that of normal ones (kappa= 1.174+/-0.134) (P<0.001). Both approaches demonstrated that diabetes can indeed impair the temporal coordination between neuronal spiking and slow oscillation of population activity in hippocampus. This observed neural coordination impairment may serve as a network level mechanism for diabetes-induced memory deterioration.
Action Potentials ; Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Hippocampus ; physiopathology ; Memory ; Oscillometry ; Rats

The changes in excitability and autorhthmicity of bladder detrusor in experimental non-insulin dependent diabetes mellitus (NIDDM) rats were observed. Sixty-nine NIDDM rats as NIDDM group and 69 normal rats as control group were enrolled into this experimental study. At 6th, 10th, 14th, 18th, 22nd and 26th week after the rats were injected last time, the changes in the excitability and autorhthmicity of detrusor strips in vitro were observed. The results showed that the threshold of the tension which made the detrusor strips contract was significantly higher in NIDDM group (0.716 +/- 0.325 g) than in control group (0.323 +/- 0.177 g) (F = 59.63, P < 0.001). At different stages, the threshold of the tension resulting the contract of the detrusor strips in NIDDM group was also higher than in control group. At 18th week after STZ injection, the frequency of spontaneous contract of the detrusor strips in NIDDM was significantly higher than in control group (P < 0.05), whereas at 22nd week, that in NIDDM group was significantly lower than in control group (P < 0.05). It was concluded that the decreased excitability of the bladder detrusor was the earliest and most obvious changes in bladder function in diabetes rats and the autorhthmicity had also changed at the early stage of diabetic bladder.
Diabetes Mellitus, Experimental/*physiopathology ; Diabetes Mellitus, Type 2/physiopathology ; Muscle Contraction/physiology ; Muscle Relaxation/physiology ; Rats, Wistar ; Urinary Bladder/*physiopathology ; Urinary Bladder Diseases/etiology ; Urinary Bladder Diseases/*physiopathology

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

OBJECTIVETo investigate the effect of hyperglycemia induced by different doses of strepzotozocin (STZ) on the liver, kidneys and eyes in rats.

METHODSFifty SD rats were divided equally into 5 groups to receive intraperitoneal injections with a single dose of STZ (40, 50, or 60 mg/kg), 3 doses of 25 mg/kg STZ (given at the interval of 24 h), or no treatment (blank control). The dynamic change of blood glucose was observed within 72 h after the first injection. Blood glucose was then monitored every 3 days and the general conditions of the rats were recorded. In the 9th week, fasting blood samples were collected for biochemical analysis and the pancreas, kidney, liver, and eye were examined for pathologies.

RESULTSWithin 72 h after STZ injection, blood glucose first slightly increased and then decreased and again increased to maintain a high level. Death occurred in rats receiving injections with 50 and 60 mg/kg STZ on the third day. In the surviving rats in the 4 STZ-injected groups, the success rate of modeling was 70%, 89%, 100%, and 100%, respectively. Blood glucose showed an inverse correlation with the body weight of the rats. Cataract was observed in the 10th week in rats injected with 40 mg/kg STZ and in the 8th week in the other groups. In the 9th week, the rats receiving 40 mg/kg STZ showed normal insulin, C-peptide, urea, UA, Cr, ALT, AST, TP, and ALB levels, but the rats in the other groups all showed variations in these biochemical indices, which corresponded to the pathological findings in the pancreas, kidneys, and liver.

CONCLUSIONSThree STZ doses of 25 mg/kg is optimal and efficient for inducing diabetes in rats with stable hyperglycemia. Both fasting and random blood glucose tests contribute to the evaluation of the complications of diabetes. The eyes are the most sensitive to hyperglycemia, followed by the kidneys and then by the liver.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Experimental ; physiopathology ; Eye ; physiopathology ; Hyperglycemia ; physiopathology ; Kidney ; physiopathology ; Liver ; physiopathology ; Pancreas ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

This study aimed to explore the cognitive dysfunction of and hippocampal neuron damage to Wistar rats with STZ-induced diabetes at different morbidity time. All Wistar rats in the tests received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes. The concentration of blood glucose and the body weight were investigated, the cognitive ability of rats was assessed using a standardized Y-maze, and the apoptotic neurons in the CA1 of the hippocampus were also examined by using the HE staining. While the sickening time was prolonged, the blood glucose concentration of the experimental rats increased continuously and the body weight decreased. On the 70th day after STZ administration, the neuronal loss in the hippocampal CA1 region increased and the working errors increased in rats with the diabetes. The results showed that Wistar rats could complicate with diabetic encephalopathy in 70 days after injection of STZ for inducing the diabetes.
Animals ; Blood Glucose ; Body Weight ; CA1 Region, Hippocampal ; cytology ; pathology ; Cognition ; Cognition Disorders ; physiopathology ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 1 ; Neurons ; pathology ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVETo get a better understanding of the mechanisms underlying type 1 diabetes mellitus, the differentially expressed pancreatic proteins from multiple low-dose streptozotocin (MLD-SIZ) mouse and normal mouse were analyzed and compared.

METHODS20 male rats were separated into 2 groups (n=10): model mice treated with MLD-STZ and normal mice,differences of pancreatic proteome among in the two groups of mice, were analyzed by two dimensional polyacryamide gel electrophoresis (2DE). Protein quantification was analyzed and the differentially expressed spots were identified using mass spectrometry and MASCOT database searching.

RESULTSCompared with control group, 23 proteins had changed significantly in the model group, 8 proteins expression were up-regulated, 15 proteins expressions down-regulated significantly. Using MALDI-TOF-MS, 15 proteins with significant change were identified by peptide fingerprinting map and the results were searched in MASCOT database. The function analyzed showed that proteins with change were associated with metabolic, anti-oxidant, structural, catalytic enzymes and chaperone, et al.

CONCLUSIONType 1 diabetes is probably exerted via multi-target and multi-path mechanism. The proteins with significant change are newly target for type 1 diabetes early diagnosis and treatment.

Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 1 ; chemically induced ; metabolism ; physiopathology ; Male ; Mice ; Pancreas ; metabolism ; Proteins ; metabolism ; Proteomics ; methods ; Streptozocin

OBJECTIVETo investigate the effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats.

METHODSForty Sprague-Dawley (SD) rats were divided into 4 groups: diabetes group; diabetes and ablation of left sympathetic nerve group; diabetes and metoprolol group and sham group. The diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The ventricular diastolic effective threshold (DET), effective refractive period (ERP), and Ventricular fibrillation threshold (VFT) were measured. The serum concentration of nerve growth factor (NGF) was measured.

RESULTSMetoprolol increased DET of ischemic and anoxic myocardium in diabetic rats. The ablation of the left sympathetic nerve increased VFT of diabetic rats. VFT in metoprolo group was significantly increased compared to diabetes group after ischemia. The concentrations of NGF in diabetic group and metoprolol group were higher than those in sham group. There were no difference in NGF levels between ablation of left sympathetic nerve group and sham group.

CONCLUSIONThe remodeling of sympathetic nerve affects the electrophysiology of ischemic myocardium of diabetic rats. Metoprolol can increase the VFT and decrease the excitation threshold of the ischemic myocardium in diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Heart ; drug effects ; physiopathology ; Male ; Metoprolol ; pharmacology ; Myocardial Ischemia ; physiopathology ; Nerve Growth Factor ; blood ; Rats ; Rats, Sprague-Dawley ; Sympathectomy

This project was designed to investigate the role of angiotensin converting enzyme 2 (ACE2) in the diabetic renal injury by observing the expression of ACE2 in the kidney and the level of angiotensin II (AngII) in the circulatory system and kidney tissue of rats with diabetes. SD rats were randomly divided into control group and diabetes group. Diabetic nephropathy model was established by i.p. injection of streptozotocin (STZ). The rats were sacrificed separately on the 15th or 30th day after STZ injection. Biochemical parameters including blood glucose and renal function were examined. The expression of ACE2 in the kidney was detected by real-time PCR and Western blot. The contents of AngII in plasma and kidney were detected by radioimmunoassay. The results are as follows: (1) 48-72 h after STZ injection, the rats showed polyuria, polydipsia and their activity reduced. (2) Blood glucose levels were 4.9-6.5 mmol/L in the control rats, 14.0-17.5 mmol/L in the diabetes group rats on the 15th day, and higher than 24 mmol/L in the diabetes group rats on the 30th day; (3) There was a significant increase of urine glucose level (P < 0.05), and a slight but not significant increase of urine protein level (P > 0.05) in the diabetes group on the 15th day; On the 30th day, the levels of urine glucose and urine protein were significantly higher than those in the control group (P < 0.01); (4) Compared with the control group, the expression of ACE2 mRNA was slightly increased (P > 0.05), and the expression of ACE2 protein was significantly increased (P < 0.05) in the rats of diabetic model group on the 15th day; however, on the 30th day, ACE2 mRNA expression in the rats of diabetic model group was significantly lower than the control group (P < 0.05), and the expression of ACE2 protein was slightly lower than the control group (P = 0.0718). (5) Compared with the control group, the levels of AngII in plasma and kidney of the diabetic rats increased slightly on the 15th day (P > 0.05); while the AngII levels in diabetic model group rats were significantly higher (P < 0.05) than that in control rats on the 30th day. These results suggest that ACE2 plays a positive role in the protection against the pathogenesis of early renal damage. ACE2 expression is reduced gradually with the deepened degree of diabetic kidney damage, leading to the accumulation of AngII in the kidney, thereby increasing the renal injury.
Angiotensin II ; blood ; metabolism ; Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; enzymology ; physiopathology ; Diabetic Nephropathies ; enzymology ; physiopathology ; Kidney ; enzymology ; physiopathology ; Peptidyl-Dipeptidase A ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo examine the renal function changes and mechanisms on rats with diabetes through a sleeve gastrectomy operation.

METHODSThirty-six rats were induced diabetes through injection of streptozotocin (STZ), and 30 of these diabetic rats that blood glucose levels at the midrange (blood sugar 17.88-23.65 mmol/L, mean: 20.32 mmol/L) were randomly assigned to the sleeve gastrectomy group, Sham-operation group and control group. The serum creatinine, lipid parameters were measured postoperatively. The 24 h urine volume obtained and urine albumin excretion rate (UAER) was calculated. Serum and urinary creatinine were examined and glomerular filtration rate (GFR) was counted. Kidney sections were stained with periodic acid-Schiff, and then the index of mesangial expansion was determined. The expression of synaptopodin for podocytes was also performed through the immunohistochemical procedure. A one-way ANOVA and t-test were performed to evaluate differences between groups and each other.

RESULTSOnly one rat of SG group died after operation. The GFR ((8.44 ± 2.10) ml · g⁻¹ · d⁻¹), 24 h UAER ((36.04 ± 11.10) mg/d), plasma lipids level (total cholesterol (1.66 ± 0.23) mmol/L, triglycerides (1.25 ± 0.17) mmol/L), kidney weight ((1.61 ± 0.06) g), the index of mesangial expansion ((6.14 ± 1.50)%) and synaptopodin expression ((20.44 ± 2.99)%) were improved in the SG group compared with the sham-operation group ((15.05 ± 3.01) ml · g⁻¹ · d⁻¹, (57.01 ± 11.34) mg/d, (2.15 ± 0.29) mmol/L, (1.65 ± 0.23) mmol/L, (1.93 ± 0.07) g, (11.32 ± 2.09)%, (10.34 ± 1.43)%) and control group ((14.79 ± 2.38) ml · g⁻¹ · d⁻¹, (62.71 ± 16.46) mg/d, (2.23 ± 0.21) mmol/L, (1.59 ± 0.20) mmol/L, (1.91 ± 0.06) g, (10.82 ± 1.79)%, (11.13 ± 2.43)%) (t = 0.781-5.025, all P < 0.05).

CONCLUSIONThe sleeve gastrectomy procedure can improve the renal function in a diabetes rat model may be through protecting the podocytes function and preventing the mesangial expansion of glomeruli.

Animals ; Blood Glucose ; Creatinine ; blood ; urine ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetic Nephropathies ; physiopathology ; surgery ; Gastrectomy ; Glomerular Filtration Rate ; Kidney ; physiopathology ; Kidney Function Tests ; Random Allocation ; Rats

OBJECTIVETo determine whether mobilized peripheral blood mononuclear cells (M-PBMNCs) obtained from patients with diabetes was impaired in therapeutic neovascularization in limb ischemia, and to explore the pathological mechanisms of the impairment.

METHODSEndothelial progenitor cells (EPC) were cultured in EGM-2MV, and then characterized by uptake of 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Dil-AcLDL) and binding of ulex europaeus agglutinin (UEA). The number of EPC was compared between M-PBMNCs obtained from diabetic patients and those from normal subjects. M-PBMNCs obtained from diabetic patients, M-PBMNCs obtained from normal controls, or PBS were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion was detected by laser Doppler blood perfusion imaging between these three groups in the following 1, 3, 7, 14, 21, and 28 days. Ambulatory score and ischemia damage were evaluated in the following 4 weeks. Capillary/fiber ratio was detected by CD31 or BS-1 lectin, and arteriole density was detected by alpha-smooth muscle actin (alpha-SMactin).

RESULTSThe number of EPC from diabetic patients were positively correlated with the blood perfusion (R = 0.486, P < 0.05) and capillary density (R = 0.491, P < 0.05), and the EPC number in diabetic patient were negatively correlation with their disease courses (R = - 0.587, P < 0.05). Transplantation of diabetic M-PBMNCs augmented the blood perfusion of ischemia hindlimbs, increased the capillary and arteriole densities, and promoted the collateral vessel formation. However, all the improvements were less significant in the diabetic patients than in the non-diabetic patients (P < 0.05).

CONCLUSIONDiabetes decreased the capability of M-PBMNCs to augment neovascularization in ischemia.

Animals ; Diabetes Mellitus ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Endothelial Cells ; physiology ; transplantation ; Extremities ; blood supply ; Humans ; Ischemia ; physiopathology ; Leukocytes, Mononuclear ; physiology ; transplantation ; Mice ; Mice, Nude ; Microvessels ; physiopathology ; Neovascularization, Physiologic ; Stem Cell Transplantation