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STZ Injection (stz + injection)
Selected AbstractsDHEA improves impaired activation of Akt and PKC ,/,-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes ratsACTA PHYSIOLOGICA, Issue 3 2009K. Sato Abstract Aim:, Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5,-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC ,/,)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. Methods:, Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway. After 1 week of STZ injection (55 mg kg,1) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). Results:, Blood glucose levels decreased significantly for 30,150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC ,/,, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC ,/,-GLUT4 pathways were blocked by a DHT inhibitor. Conclusion:, These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism-related signalling pathway via Akt and PKC ,/,-GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus. [source] Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic painFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2007Sameer Sharma Abstract Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor- , (TNF- ,) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF- , levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain. [source] Melatonin protects against streptozotocin, but not interleukin-1,-induced damage of rodent pancreatic ,-cellsJOURNAL OF PINEAL RESEARCH, Issue 3 2001Annika K. Andersson In the present study, we examined whether melatonin can protect rodent pancreatic islets against streptozotocin (STZ) and interleukin-1, (IL-1,)-induced suppression of ,-cell function. Formation of free radicals, DNA damage and extensive DNA repair leading to depletion of intracellular nicotinamide adenine dinucleotide (NAD) may mediate STZ toxicity. Activation of inducible nitric oxide synthase and nitric oxide (NO) formation may cause IL-1,-induced ,-cell impairment. We also studied the effect of melatonin against STZ-induced hyperglycemia in C57BL/Ks mice. For in vitro studies, cultured rat islets were exposed to melatonin (100 ,M,1 mM) 30 min prior to STZ (0.5 mM) or IL-1, (25 U/mL) addition. After an additional 30 min incubation with STZ, islet function and NAD content were analyzed either acutely or after 18 hr of recovery in fresh culture medium. For IL-1, experiments, islets were incubated for 48 hr with the cytokine before evaluation of islet function. We found that melatonin counteracted STZ-induced inhibition of glucose metabolism and insulin release in cultured rat islets after 18 hr of recovery. Moreover, NAD levels were higher in the melatonin-treated group at this time point. Melatonin had no effect on IL-1,-induced islet inhibition of glucose oxidation or NO formation. Diabetes induced by STZ (140 mg/kg body weight; i.v.) was effectively prevented by administration of melatonin (100 mg/kg body weight; i.p.) 30 min before STZ injection. We conclude that the protective effects of melatonin against ,-cell damage may be related to interference with DNA damage and poly(ADP-ribose) polymerase (PARP) activation rather than through effects on NO generation pathways. [source] Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometryJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2009Valéria Paula S. Fazan Abstract We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 21JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003R Bianchi Erythropoietin (EPO) has neurotrophic and neuroprotective effects and its efficacy and safety has been demonstrated in patients with ischemic stroke. We investigated its efficacy in preventing and reversing established nerve disorders in streptozotocin (STZ) diabetes. After STZ injection (60 mg/kg/ip), EPO (5000 units/kg b.w. i.p. three times a week) was started in a group of rats and continued for five weeks (prevention schedule). In another group of diabetic rats, EPO was started six weeks after STZ, continued for five weeks (therapeutic schedule). Groups of non-diabetic control rats were similarly treated. Antidromic nerve conduction velocity (NCV) in the tail was assessed at five weeks for all groups and at 11 weeks for the therapeutic schedule. Compared to non-diabetic rats, NCV was 21% lower (P < 0.001) at five weeks in the STZ group, EPO partially prevented this decrease (14% lower than with non-diabetic controls), with a significant difference from the untreated-diabetic group (P < 0.01). After six weeks of uncontrolled diabetes, at the beginning of therapeutic EPO, NCV was reduced by 23% and after 11 weeks by 40%, EPO efficacy was confirmed. Thermal (hot plate method) and mechanical (Randall-Selitto method) nociceptive thresholds were monitored weekly throughout the study. In addition, in all groups, the density of intra-epidermal nerve fibers, which reflects possible degeneration of somatic unmyelinated fibers, was assessed in the hindpaw using protein-gene-product 9.5 immunostaining. Rats developed mechanical hyperalgesia within two weeks after STZ injection. Both the prevention and therapeutic schedules of EPO reduced diabetic hyperalgesia after two weeks of treatment, reaching statistical significance at fur, and five weeks of treatment, with no such effect in non-diabetic controls. Hindpaw thermal response latencies were significantly (P < 0.001) increased in untreated diabetic rats compared with untreated controls. EPO had no effect on these latencies in control rats but partially prevented the increase in diabetic rats, so the values were still different from controls, but significantly different from untreated diabetics at four and five weeks in both the prevention and therapeutic studies (P < 0.05). These observations extend the therapeutic utility of EPO and highlight its potential for treating established diabetic neuropathies. [source] Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocinPHYTOTHERAPY RESEARCH, Issue 4 2002Takao Kobayashi Abstract We have reported that an aqueous extract from the flowers of Inula britannica L. subsp. japonica Kitam. (IB) prevented immunologically induced experimental hepatitis in mice and suggested that the antihepatitic effect of IB is due to inhibition of IFN-, production. We then investigated the effects of IB on diabetes in mice induced by multiple low doses of streptozotocin (MLDSTZ), which is a mouse model for IFN-,-dependent autoimmune diabetes. C57BL/KsJ mice (male, 7 weeks) were provided with IB extract (500,mg/,kg/ day) in drinking water ad libitum, starting 7 days before the first STZ injection. Autoimmune diabetes was induced by MLDSTZ (40,mg/kg/day for 5 daily doses, i.p.). The IB treatment significantly suppressed the increase of blood glucose levels. Histological analysis of the pancreas showed that the degree of insulitis and destruction of ,-cells were reduced by IB treatment. The IFN-, production from stimulated splenic T lymphocytes was inhibited by the IB treatment. Moreover, the proportion of IFN-,-producing cells in the CD4+ population, which was increased by MLDSTZ, was significantly decreased by the IB treatment. These results suggest that IB has a preventative effect on autoimmune diabetes by regulating cytokine production. Copyright © 2002 John Wiley & Sons, Ltd. [source] Inhibition of the formation or action of angiotensin II reverses attenuated K+ currents in type 1 and type 2 diabetesTHE JOURNAL OF PHYSIOLOGY, Issue 1 2001Yakhin Shimoni 1Transient and sustained calcium-independent outward K+ currents (It and ISS) as well as action potentials were recorded in cardiac ventricular myocytes isolated from two models of diabetes mellitus. 2Rats injected (i.v.) with streptozotocin (STZ, 100 mg kg,1) 6,10 days before cell isolation developed insulin-dependent (type 1) diabetes. It and ISS were attenuated and the action potential prolonged. Incubation of myocytes (6-9 h) with the angiotensin II (ATII) receptor blockers saralasin or valsartan (1 ,m) significantly augmented these currents. Inclusion of valsartan (1 g l,1) in the drinking water for 5,10 days prior to and following STZ injection partially prevented current attenuation. 3Incubation of myocytes from STZ-treated rats (6-9 h) with 1 ,m quinapril, an angiotensin-converting enzyme (ACE) inhibitor, significantly augmented It and ISS and shortened the ventricular action potential. It augmentation was not due to changes in steady-state inactivation or in recovery from inactivation. No acute effects of quinapril were observed. 4The effects of quinapril and valsartan were abolished by 2 ,m cycloheximide. 5Myocytes were isolated from the db/db mouse, a leptin receptor mutant that develops symptoms of non-insulin-dependent (type 2) diabetes. K+ currents in these cells were also attenuated, and the action potentials prolonged. Incubation of these cells (> 6 h) with valsartan (1 ,m) significantly enhanced the transient and sustained outward currents. 6These results confirm recent suggestions that cardiac myocytes contain a renin-angiotensin system, which is activated in diabetes. It is proposed that chronic release of ATII leads to changes in ionic currents and action potentials, which can be reversed by blocking the formation or action of ATII. This may underlie the proven benefits of ATII receptor blockade or ACE inhibition in diabetes, by providing protection against cardiac arrhythmias. [source] | |||||||||||||