Previous studies have shown that oxidative stress and corporal fibrosis in penile tissues of rats were key pathological factors of erectile dysfunction induced by diabetic mellitus (DMED). Lipoxin A4 (LXA4) was reported to inhibit oxidative stress and fibrosis diseases, while whether it could exert a protective role on erectile function was not clear. Type I diabetic mellitus (DM) was induced in thirty male 10-week-old Sprague-Dawley rats using streptozotocin. Ten weeks later, twenty-two rats with DMED confirmed by an apomorphine test were divided into two groups: the DMED group (n = 11) and the DMED + LXA4 group (n = 11; LXA4 injection daily for 4 weeks). In addition, another ten age-matched rats formed the Control group. We found that erectile function was significantly impaired in the DMED group compared with the Control group, but was improved in the DMED + LXA4 group. Similarly, the over-activated oxidative stress and impaired endothelial function in the DMED group were both improved in the DMED + LXA4 group. Moreover, the DMED group showed serious corporal fibrosis, which was also inhibited by the treatment of LXA4 in the DMED + LXA4 group. Taken together, LXA4 could exert an inhibition role on oxidative stress and fibrosis to improve DMED effectively.
Actins/metabolism* ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Diabetes Mellitus, Experimental/physiopathology* ; Diabetes Mellitus, Type 1/physiopathology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Lipoxins/pharmacology* ; Male ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Oxidative Stress/drug effects* ; Penile Erection/drug effects* ; Penis/pathology* ; Rats ; Rats, Sprague-Dawley

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 observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf.

METHODSThe T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (sICAM-1) were measured.

RESULTSIn comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and sICAM-1 in SHG and FHG control groups were all significantly increased (P<0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in FHG group were all significantly increased further (P<0.01 or P<0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in PQS and MHC groups were all decreased significantly (P<0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment.

CONCLUSIONBlood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.

Animals ; Aorta ; drug effects ; pathology ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Endothelin-1 ; blood ; Endothelium, Vascular ; drug effects ; physiopathology ; Hepatocyte Growth Factor ; blood ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Nitric Oxide ; blood ; Panax ; chemistry ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rats ; Saponins ; pharmacology ; therapeutic use ; Solubility ; Tumor Necrosis Factor-alpha ; blood

Foot ulcers increase morbidity and mortality in diabetic patients. Due to poor healing factors, surgical wound healing is questionable in diabetic patients. We report a patient with insulin-dependent diabetes mellitus, sensory neuropathy and microangiopathy, who had an infected stump of the right three middle digits and subsequent transmetatarsal amputation. The infected postoperative ulcer was treated with complex phototherapy, including laser and ultraviolet C (UVC) radiations. A total of 23 sessions of low-intensity laser therapy and UVC irradiation were administered over a five-week period. The infected surgical wound healed completely. During the three-month follow-up period, there was no recurrence of the ulcer, although the patient's metabolic profile remained unstable. Multimodal therapy combining UVC and laser may constitute a useful and side-effect-free alternative treatment modality for the induction of wound healing post metatarsal amputation in patients with unhealed diabetic ulcers.
Amputation ; adverse effects ; Diabetes Complications ; surgery ; Diabetes Mellitus, Type 1 ; physiopathology ; surgery ; Diabetic Foot ; physiopathology ; surgery ; Diabetic Neuropathies ; physiopathology ; Humans ; Laser Therapy ; methods ; Lasers ; Male ; Metatarsal Bones ; physiopathology ; Middle Aged ; Phototherapy ; methods ; Postoperative Complications ; therapy ; Time Factors ; Ultraviolet Rays ; Wound Healing ; Wound Infection ; therapy

Blood Glucose ; metabolism ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; physiopathology ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; physiopathology ; Dinoprost ; analogs & derivatives ; blood ; Glucose ; metabolism ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Oxidative Stress

BACKGROUNDDiabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca(2+)-activated K(+) (BK) channel activities in coronary dysfunction in streptozotocin-induced diabetic rats.

METHODSUsing videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats.

RESULTSBK currents (defined as the iberiotoxin-sensitive K(+) component) contribute (65 ± 4)% of the total K(+) currents in freshly isolated coronary smooth muscle cells and > 50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca(2+) is impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel b(1) subunit activator) robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca(2+) and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 mmol/L Ca(2+). Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-b(1) protein expression in diabetic vessels, without altering the BK channel α-subunit expression. Although the cytosolic Ca(2+) concentration of coronary arterial smooth muscle cells was increased from (103 ± 23) nmol/L (n = 5) of control rats to (193 ± 22) nmol/L (n = 6, P < 0.05) of STZ-induced diabetic rats, reduced BK-b(1) expression made these channels less sensitive to intracellular Ca(2+), which in turn led to enhanced smooth muscle contraction.

CONCLUSIONSOur results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-b(1) expression and reduction of the b(1)-mediated BK channel activation in diabetic vessels.

Animals ; Blotting, Western ; Coronary Vessels ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; physiopathology ; Diabetes Mellitus, Type 1 ; metabolism ; physiopathology ; Electrophysiology ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Male ; Muscle, Smooth, Vascular ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects and underlying mechanisms of Panax notoginoside (PNS) on the nephropathy in rats with type 1 diabetes.

METHODSA murine model of diabetic nephropathy was set up by an intravenous injection of streptozotocin (STZ). Wistar rats were randomly divided into 5 groups: the control group, the diabetic group (DM), the group treated with low-dosage PNS (PNS-L), the group treated with high-dosage PNS (PNS-H) and the group treated with catopril. Rats in the PNS-L and PNS-H groups were given different dosages of PNS while rats in the catopril group were given catopril through gastrogavage every day for the next four consecutive weeks. Serum creatinine (Cr) levels, endogenous creatinine clearance rate (CCr), and 24-h urinary microalbumin (UAlb) were examined and calculated. Meanwhile, immunohistochemistry was applied to determine the expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-7 (BMP-7) in the kidney tissue.

RESULTSThe levels of Cr, Ccr, and UAlb were all elevated significantly in the DM group (P<0.01). The expression of VEGF protein was increased but BMP-7 protein was decreased in the kidney tissue (P<0.01). However, the above items decreased in the PNS-L, PNS-H and catopril groups compared with the DM group (P<0.05, P<0.01). In the PNS-L, PNS-H and catopril groups, the expression of VEGF protein was decreased but BMP-7 protein was increased in the kidney tissue (P<0.05, P<0.01).

CONCLUSIONPNS shows protective effects on the kidney in type 1 diabetic rats at the early stage. The protective mechanism might be closely related to its role of inhibiting the expression of VEGF protein and enhancing the expression of BMP-7 protein in the kidney.

Animals ; Body Weight ; drug effects ; Bone Morphogenetic Protein 7 ; metabolism ; Diabetes Mellitus, Type 1 ; complications ; drug therapy ; pathology ; physiopathology ; Diabetic Nephropathies ; complications ; drug therapy ; pathology ; physiopathology ; Hypertrophy ; Immunohistochemistry ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Function Tests ; Male ; Panax ; chemistry ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Proteinuria ; complications ; drug therapy ; pathology ; physiopathology ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; metabolism

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

BACKGROUNDDiabetic nephropathy is a major cause of renal failure in diabetes mellitus (DM). It has been known that renin-angiotensin system (RAS) blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin II receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin (STZ)-induced DM rats.

METHODSDM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment (OLM + DM) group. The normal group (non-DM) were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated: slope of flow-pressure (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature), slope of pressure-GFR (glomerular filtration capacity against pressure) and threshold pressure for beginning filtration at pressure-GFR (preglomerular to postglomerular vascular resistance ratio). Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.

RESULTSThe body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight, urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM + DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats (P < 0.05). But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats (P < 0.05) with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan (P < 0.05). Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats (P < 0.05). The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.

CONCLUSIONSTreatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Diabetic Nephropathies ; drug therapy ; prevention & control ; Hemodynamics ; drug effects ; Imidazoles ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Organ Size ; drug effects ; Rats ; Rats, Wistar ; Tetrazoles

OBJECTIVE: To investigate the contralateral suppressions of transient evoked otoacoustic emissions (TEOAE) in diabetes mellitus patients with normal hearing. METHOD: The pure tone audiometry, acoustic immittance and TEOAE tests were performed in 30 diabetes mellitus patients with normal hearing and 30 healthy controls. The efferent system functions were evaluated by contralateral suppression of TEOAE. RESULT: There were no significant differences of pure tone thresholds and amplitudes of TEOAE between the two groups. The contralateral suppressions of TEOAE in diabetes mellitus patients were significantly lower than that in controls (P<0.05 at 2000 and 4000 Hz respectively). CONCLUSION The nerve functions of central nerve system can be damaged in diabetes mellitus patients with normal hearing.
Adolescent ; Adult ; Audiometry, Pure-Tone ; Auditory Threshold ; Child ; Diabetes Mellitus, Type 1 ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Otoacoustic Emissions, Spontaneous ; Young Adult