Protective effect of Lycium barbarum polysaccharide 4 on kidneys in streptozotocin-induced diabetic rats

2009 ◽  
Vol 87 (9) ◽  
pp. 711-719 ◽  
Author(s):  
Rui Zhao ◽  
Qing-wang Li ◽  
Jian Li ◽  
Tao Zhang
Keyword(s):  
Protective Effect ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Protective Mechanism ◽  
Lycium Barbarum ◽  
Physiological Level ◽  
Extracellular Signal ◽  
Lycium Barbarum Polysaccharide

Lycium barbarum polysaccharide (LBP) has been shown to have hypoglycemic and antioxidative properties, although its mode of action is yet unknown. Because oxidative stress is implicated in the pathogenesis of diabetic nephropathy, we evaluated the protective effect of LBP-4, the major active component of Lycium barbarum, on the defensive antioxidative mechanism in kidneys in a streptozotocin-induced diabetic rat model. Moreover, we investigated the effects of LBP-4 on the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in isolated mesangial cells. The role of protein kinase C (PKC)-dependent and -independent pathways in LBP-4-reduced ERK1/2 was studied by bisindolylmaleimide (BIM) IV, an inhibitor of PKC. Diabetic rats treated with LBP-4 (10 mg/kg) for 8 weeks showed increased activity of antioxidant enzymes and increased scavenging of oxygen radicals, while the activity of PKC in the renal cortex was maintained at a physiological level. The decreased activation of ERK1/2 in mesangial cells, through the involvement of PKC, could explain the protective mechanism in kidneys of diabetic rats treated with LBP-4.

Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy

1997 ◽  
Vol 272 (1) ◽  
pp. R259-R267 ◽  
Author(s):  
K. T. McVary ◽  
C. H. Rathnau ◽  
K. E. McKenna
Keyword(s):  
Sexual Function ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
Diabetic Rat ◽  
Penile Erections ◽  
Reflex Testing ◽  
Diabetic Impotence ◽  
Central Neuropathy ◽  
Sexual Reflexes

The pathophysiological mechanisms of diabetic impotence remain obscure. We have presented an analysis of sexual function in a diabetic rat (BB/WOR) model characterized by diffuse neuropathic changes without a confounding vasculopathy that allows us to define the neural components of erectile failure. Copulatory behavioral testing demonstrated that diabetic males were severely impaired: the controls mounted three times more than the diabetics and had about one-half the latency to first mount. The diabetics had about one-fourth the number of intromissions and took nearly twice as long to achieve first ejaculation. The number of ejaculations was drastically reduced as well. We examined sexual reflexes in the anesthetized acutely spinalized rat. These experiments tested the integrity of spinal circuits controlling sexual function. Reflex testing demonstrated that spinal sexual reflexes were also severely impaired: the onset latency of reflexes was more than doubled, and the duration of reflexes was less than one-half. More than one-half of the diabetic rats showed no penile erections. Neural studies showed even more derangement in reflex measures in rats, without erection. Nerve conduction velocity experiments suggested a peripheral neuropathic change in hypogastric nerve and motor pudendal nerve fibers. These dysfunctional findings were seen without any androgen deficiency. These results indicate that diabetic impotence in this model reflects central and peripheral neuropathic disease processes.

Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin

1990 ◽  
Vol 68 (6) ◽  
pp. 914-921 ◽  
Author(s):  
Eduardo T. Cánepa ◽  
Elena B. C. Llambías ◽  
Moisés Grinstein
Keyword(s):  
Aminolevulinic Acid ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Significant Inhibition ◽  
Diabetic Rat ◽  
Experimental Conditions ◽  
Cytochrome P 450

In the present work we demonstrate that insulin decreases the phenobarbital-induced activities of δ-aminolevulinic acid synthase and ferrochelatase in isolated hepatocytes from normal and experimental-diabetic rats. Insulin concentrations required to produce significant inhibition in diabetic hepatocytes were higher than in normal cells. Under similar experimental conditions, insulin decreased the basal activities of δ-aminolevulinic acid synthase and ferrochelatase in hepatocytes from normal rats; no inhibitory effect was observed on the basal activity of δ-aminolevulinic acid synthase in hepatocytes from diabetic rats. Cytochrome P-450 content of both normal and diabetic cells was not affected by insulin in absence or presence of phenobarbital. The inhibitory action of insulin was exerted even when effective concentrations of glucagon, dexamethasone, or 8-(p-chlorophenylthio)-cAMP were present.Key words: δ-aminolevulinic acid synthase, ferrochelatase, cAMP, insulin, diabetic rat hepatocytes.

Reduced conduction reserve in the diabetic rat heart: role of iPLA2 activation in the response to ischemia

2011 ◽  
Vol 300 (1) ◽  
pp. H326-H334 ◽  
Author(s):  
Parisa Rahnema ◽  
Yakhin Shimoni ◽  
Anders Nygren
Keyword(s):  
Conduction Velocity ◽  
Electrical Coupling ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Acute Ischemia ◽  
Cellular Excitability ◽  
Bromoenol Lactone ◽  
Healthy Control ◽  
Time To Onset

Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca2+-independent phospholipase A2 (iPLA2) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA2 activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA2 activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA2 activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.

scholarly journals Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasmin Chendi Li ◽  
Anida Velagic ◽  
Cheng Xue Qin ◽  
Mandy Li ◽  
Chen Huei Leo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitrogen Oxide ◽  
Carotid Arteries ◽  
Body Weight Gain ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Endothelium Dependent Relaxation

Introduction:Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.

(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis

2020 ◽  
Vol 319 (4) ◽  
pp. F571-F578
Author(s):  
Maki Urushihara ◽  
Shuji Kondo ◽  
Yukiko Kinoshita ◽  
Natsuko Ozaki ◽  
Ariunbold Jamba ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Mesangial Cells ◽  
Macrophage Infiltration ◽  
Crescent Formation ◽  
Sirna Treatment ◽  
Extracellular Signal ◽  
Parietal Epithelial Cells

(Pro)renin receptor [(P)RR] has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of the present study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. The anti-glomerular basement membrane nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (percent glomerular crescent: 62.1 ± 2.3%) accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4, and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4, and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-glomerular basement membrane nephritis and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR.

On the Protective Effect of Lycium Barbarum Polysaccharide (LBP) on Optic Nerve Tissue and Retinal Ganglion Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 443-448
Author(s):  
Shuzhen Wang ◽  
Zelin Xu ◽  
Yuanyuan Zhao ◽  
Chao Liu
Keyword(s):  
Optic Nerve ◽  
Optic Neuritis ◽  
Protective Effect ◽  
Intrathecal Injection ◽  
Nerve Damage ◽  
Nerve Tissue ◽  
Blue Staining ◽  
Lycium Barbarum ◽  
Optic Nerve Damage ◽  
Lycium Barbarum Polysaccharide

Background: The present paper established a model of optic neuritis injury by intrathecal injection of lipopolysaccharide (LPS) into the optic nerve, then explored the protective effect of Lycium Barbarum Polysaccharide (LBP) on optic nerve tissue and RGCs after injury. Material and methods: LPS was microinjected into the optic nerve of SD rats to induce optic neuritis. The histopathological variations of HE staining were observed in each group. The expressions of ED1/CD68 and GFAP were determined by immunofluorescence. The optic nerve repairment was evaluated by lux solid blue staining. TUNEL detects retinal cell apoptosis. Western blot was used to detect differences in expressions of related proteins. Results: LBP can alleviate the degree of optic nerve damage in rats with optic neuritis injury, inhibit the increase of LPS-induced macrophages and astrocytes in the optic nerve and retina, mitigate LPS-induced retinal RGC damage, inhibit LPS-induced expressions of proinflammatory cytokines TNF-α and IL-6, COX2 and iNOS in the optic nerve injury model of optic neuritis in rats, as well as inhibit the activation of STAT1, STAT3 and NF-κB pathways. Conclusion: LBP can ameliorate optic nerve damage, and the mechanism may be realized through inhibiting NF- B and STAT signaling pathways.

Reduced IP receptors in STZ-induced diabetic rat kidneys and high-glucose-treated mesangial cells

2004 ◽  
Vol 287 (4) ◽  
pp. F673-F681 ◽  
Author(s):  
Rania Nasrallah ◽  
Richard L. Hébert
Keyword(s):  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β ◽  
Diabetic Rats ◽  
Receptor Protein ◽  
Matrix Metalloproteinase 2 ◽  
Diabetic Rat ◽  
Leucine Incorporation ◽  
Outer Medulla ◽  
Key Enzyme

Mesangial cells (MG) are an important source of renal PGE2 and PGI2. The purpose of this study was to examine the effects of cicaprost (CCP; PGI2 analog) on MG function and the expression of IP receptors in streptozotocin (STZ)-diabetic rats and glucose-treated MG cells. CCP increased cellular cAMP in immortalized rat MG cells. Both glucose and anisomycin attenuated CCP-cAMP, but not PMA, angiotensin II, or transforming growth factor-β. Also, IP receptor protein was reduced in response to glucose. While CCP decreased the levels of the cell cycle inhibitor p27, it did not alter thymidine or leucine incorporation. However, CCP reduced fibronectin levels by 40% and increased matrix metalloproteinase-2 levels threefold, a key enzyme in matrix degradation. Finally, IP receptors were significantly reduced in the outer medulla of 4- and 12-wk STZ-diabetic rats and in the cortex, outer, and inner medullary regions in 6-mo uninephrectomized STZ-diabetic rats. The changes in the CCP/IP system observed in this study suggest that IP may serve as an alternate therapeutic target in diabetes.

Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis

1998 ◽  
Vol 274 (6) ◽  
pp. E984-E991 ◽  
Author(s):  
Firas Saker ◽  
Juan Ybarra ◽  
Patrick Leahy ◽  
Richard W. Hanson ◽  
Satish C. Kalhan ◽  
...  
Keyword(s):  
Cobalt Chloride ◽  
Glucose Production ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Lowering Effect ◽  
Significant Decrement ◽  
Camp Levels

Results of previous studies indicated that treatment of diabetic rats (induced by streptozotocin) with cobalt chloride (CoCl2) resulted in a significant decrement in serum glucose concentration. The present study was designed to determine the potential role of enhanced glucose uptake vs. decreased glucose production in the above response. The rate of systemic appearance of glucose, measured under fasting conditions using [3-3H]glucose tracer, was reduced from 35.5 ± 2.5 to 17.5 ± 1.8 μmol ⋅ kg−1 ⋅ min−1in diabetic rats treated with 2 mM CoCl2 added to the drinking water for 10–14 days ( P < 0.01). Tissue accumulation of intravenously administered 2-deoxy-[14C]glucose was significantly reduced in kidney and eye of diabetic rats treated with CoCl2, whereas the uptake remained unchanged in several other tissues including cerebrum, red and white skeletal muscle, heart, and liver. The relative content of phospho enolpyruvate carboxykinase (PEPCK) mRNA was increased 3.1-fold in livers of diabetic compared with normal rats ( P < 0.001), and treatment of diabetic rats with CoCl2 decreased hepatic PEPCK mRNA levels to normal. The content of PEPCK mRNA in the liver was decreased by 33% in CoCl2-treated normal rats ( P < 0.05). Treatment with CoCl2 resulted in no change in cAMP levels in the livers of either diabetic or normal rats. These results suggest that the glycemia-lowering effect of CoCl2 is mediated by reductions in the rate of systemic appearance of glucose and hepatic gluconeogenesis.

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