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 ; Diabetes Mellitus, Experimental/blood/*complications/pathology ; Disease Models, Animal ; Hyperkalemia/*complications ; Hypoaldosteronism/*complications ; Kidney Tubules, Distal/ultrastructure ; Male ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Zona Glomerulosa/ultrastructure

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

OBJECTIVETo compare the apoptosis and hemodynamic changes of the penile tissue in diabetic and healthy rats.

METHODSSixteen chronic diabetic and 10 matched normal control rats were injected with a single dose of streptozotocin (STZ) 65 mg/kg and the diabetic model established. Eight weeks later the rats were killed, their haemoglobin Alc( HbAlc) measured, and their penises harvested. TUNEL assay (in situ nick end-labeling) and flow cytometry were used to analyse the penile cells for apoptosis. The thickness and diameter of the arteries were measured.

RESULTSTUNEL showed apoptosis in the chronic diabetic rats. Flow cytometric analysis showed the apoptotic peak in the penile cells of the chronic diabetic rats when compared with the controls (P < 0.05). There was significant difference between the diabetic and healthy rats. Morphological analysis revealed that the thickness of the artery wall increased while the artery diameter decreased in the diabetes group compared with the controls.

CONCLUSIONDiabetes can lead to increasing apoptosis of the penile tissue, cause a decrease in the penile artery diameter and the thickening of the penile artery wall.

Animals ; Apoptosis ; Arteries ; pathology ; Diabetes Mellitus, Experimental ; complications ; pathology ; physiopathology ; Erectile Dysfunction ; etiology ; Flow Cytometry ; In Situ Nick-End Labeling ; Male ; Penis ; blood supply ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood

OBJECTIVETo observe the effect of heart protection on diabetic cardiomyopathy in rats by tripterysium glucosides.

METHODThe rat diabetic cardiomyopathy rats model are made by streptozotocin, then divided into tripterysium glucosides group (n=8) and model group (n=8). In addition, the control group is established (n=8). Glucosides group was orally administrated tripterysium glucosides (18 mg x kg(-1)), the control groups was orally administrated same volume NS for 3 months. Blood sugar, heart function and cardiac index were detected after 3 months. Immunohistochemical techniques were used to detect NF-kappaB and ICAM-1 expression. Ultrastructure of cardiac muscle cell were observed by electronmicroscope.

RESULTCompared with model group, cardiac index was decreased after tripterysium glucosides administration, and LVSP, LVEDP, + dp/dtmax, -dp/dtmax, were improved, and the expression of nuclear Factor-kappaB (NF-kappaB) and intercellular adhension molecule-1 (ICAM-1) was inhibited. Ultrastructure of cardiac muscle cell such as mitochondrion and cardiac muscle fibers was atttenuated.

CONCLUSIONTripterysium glucosides could protect rat diabetic cardiomyopathy rats heart. These function may be related to inflammatory reaction inhibition and immunosuppression of tripterysium glucosides.

Animals ; Blood Glucose ; metabolism ; Cardiomyopathies ; etiology ; metabolism ; pathology ; physiopathology ; Diabetes Mellitus, Experimental ; complications ; Gene Expression Regulation ; drug effects ; Glucosides ; administration & dosage ; pharmacology ; therapeutic use ; Heart ; drug effects ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Myocardium ; ultrastructure ; NF-kappa B ; metabolism ; Rats

OBJECTIVETo observe the the protective effection of polysaccharides-2b of mudan cortex of Paeonia suffruticosa andr (PSM2b) on diabetic cataract.

METHODThe animal model of diabetic cataract in rats was induced by streptozotocin (STZ) and freund's adjuvant complete (CFA). The initial opacity occurrence time in lens was investigated with cranny lamp, and opacity degree of lens was compared too. The activities of glutathione peroxidase (GSH-pX), superoxide dismutase (SOD), catalase (CAT), the content of malonaldehyde (MDA) in serum and lens were detected. At the same time, the activities of Na(+) -K(+) -ATPase, the content of macromolecular weight protein and infusibility protein in lens were detected too.

RESULTThe results examinated by cranny lamp showed that PSM2b could significantly postpone the occurrence and alleviate opacity degree of lens. Compared with model group, every treatment group of PSM2b could lower the level of MDA, high and middle dose groups could increase the levels of SOD, GSH-pX, CAT in serum and lens in evidence, and enhance the activity of Na(+) -K(+) -ATPase. These indexes present favorable positive correlation between dose and effect.

CONCLUSIONAll these results demonstrated that PSM2b had apparently protective effection on diabetic cataract in rats.

Animals ; Catalase ; blood ; metabolism ; Cataract ; etiology ; metabolism ; prevention & control ; Diabetes Mellitus, Experimental ; blood ; chemically induced ; complications ; Glutathione Peroxidase ; blood ; metabolism ; Lens, Crystalline ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; blood ; metabolism ; Paeonia ; chemistry ; Phytotherapy ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Streptozocin ; Superoxide Dismutase ; blood ; metabolism

Hepatocyte growth factor (HGF) is a potent mitogen and promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF, an adenoviral vector carrying the human HGF (Ad.hHGF) gene was transfected into the streptozotocin-induced diabetic mice and evaluated the effect on the blood glucose metabolism and the insulin-secreting beta cells of pancreatic islets. Ad.hHGF gene transfection resulted in amelioration of hyperglycemia and prolongation of survival period in the diabetic mice. Concomitantly adenoviral- mediated hHGF gene therapy slightly increased serum insulin concentration and the expression of insulin in the pancreatic islet. Although the proliferation of beta-cell mass was not noticeable, the beneficial effect of HGF is significant to an almost deteriorated pancreatic islets. Taken together, these data suggest that the Ad.hHGF gene therapy into diabetic mice may prevent the further destruction and present as a beneficial remedy for type 1 diabetic patients.
Adenoviridae/*genetics/physiology ; Animals ; Blood Glucose/analysis ; Body Weight ; Diabetes Mellitus, Experimental/blood/genetics/*metabolism/*therapy ; *Gene Therapy ; Hepatocyte Growth Factor/genetics/*metabolism ; Humans ; Hyperglycemia/blood/complications/genetics/*therapy ; Insulin/blood ; Islets of Langerhans/metabolism/*pathology ; Male ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/genetics/metabolism ; Survival Rate

AIMTo assess the effects of the alpha-glucosidase inhibitor Sangzhi (Ramulus mori, SZ) on the relief of diabetic symptoms of hyperglycemia and the prevention of its late complications in alloxan diabetic rats with high-calorie chow.

METHODSThe aqueous extract of Sangzhi was given orally to alloxan diabetic rats for 15 days. The hyperglycemic symptoms were observed. The blood glucose, lipid levels and the nephrotic representations were measured.

RESULTSWhen alloxan diabetic rats on high-calorie chow were treated with SZ, the hyperglycemic symptoms were improved, the blood lipid levels were improved, the ratio of kidney over body weight and the blood N-acetyl-beta-D-glucosaminidase (NAG) activity were lowered. The degree of renal pathological changes was significantly reduced.

CONCLUSIONSZ may be useful for treating diabetes and its complications.

Acetylglucosaminidase ; blood ; Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; metabolism ; Diabetic Nephropathies ; etiology ; metabolism ; prevention & control ; Disease Models, Animal ; Enzyme Inhibitors ; therapeutic use ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; isolation & purification ; pharmacology ; therapeutic use ; Kidney ; pathology ; Male ; Morus ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Triglycerides ; blood ; alpha-Glucosidases ; isolation & purification

OBJECTIVETo investigate the effect of Xuezhikang (, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism.

METHODSSixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion (UAE) measurement. Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by Western blot.

RESULTSCompared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent.

CONCLUSIONSRenal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.

Albuminuria ; blood ; complications ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; In Situ Nick-End Labeling ; Kidney ; drug effects ; pathology ; Kidney Glomerulus ; pathology ; Lipids ; blood ; Male ; Mesangial Cells ; drug effects ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats, Sprague-Dawley ; Streptozocin ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDDiabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes.

METHODSWe used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats.

RESULTSGSPE significantly reduced the AGEs of diabetic rats (P < 0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism.

CONCLUSIONSThese findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

Animals ; Blood Glucose ; drug effects ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; complications ; metabolism ; pathology ; Diabetic Retinopathy ; drug therapy ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Glycated Hemoglobin A ; metabolism ; Glycation End Products, Advanced ; metabolism ; Grape Seed Extract ; Male ; Plant Extracts ; pharmacology ; Proanthocyanidins ; pharmacology ; Proteomics ; methods ; Rats ; Rats, Wistar