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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of oral zinc supplementation on lipid peroxidation and the antioxidant defense system of alloxan (80-90 mg/kg)-induced diabetic rabbits were examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately 2.5 kg, were allocated randomly and equally as control, diabetic, and zinc-supplemented diabetic groups. After diabetes was induced, zinc-supplemented diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO(4)) in their drinking tap water for 3 months. The feed and water consumption was higher in diabetic groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic rabbits compared to control. The blood glucose levels were higher in diabetic groups than controls. The elevated plasma malondialdehyde (MDA) levels were determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin levels in the diabetic group were decreased by the effect of diabetes but there was no difference between zinc-supplemented diabetic and control rabbits. Serum zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu) levels in sera were not different among the groups. As a result, it was concluded that daily zinc supplementation could reduce the harmful effects of oxidative stress in diabetics.
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PMID:Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits. 1744 94

1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangements induced by diabetes were not affected by salt overload.
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PMID:Chronic salt loading and cardiovascular-associated changes in experimental diabetes in rats. 1758 Dec 11

Diabetes is a chronic autoimmune disease that affects 4-5% of the world's population. If the present trends continue, diabetes would soon become a major/leading health problem worldwide. Hence there is an urgent need to develop novel approaches for the treatment of diabetes. While transplantation of the pancreas or that of isolated pancreatic islets can lead to the cure of the disease in some patients, immunological complications and the chronic shortage of donors makes it impossible to adequately treat all patients. Interestingly, embryonic stem cells (ESC) have emerged as a possible source of pluripotent cells that can be coaxed into insulin-producing cells (IPCs) that can be used to treat diabetes. However, until appropriate protocols have been established, this new technology will be difficult to tap into. Our laboratory is interested in developing new strategies for harnessing the pluripotency of ESC and differentiating them into IPCs that are stable and will continue to produce insulin in vivo. A second aspect is the non-availability of non-invasive imaging protocols. We show here that transcriptionally targeted luciferase expression can be used successfully to non-invasively monitor the transplanted cells in vivo.
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PMID:Strategies for differentiating embryonic stem cells (ESC) into insulin-producing cells and development of non-invasive imaging techniques using bioluminescence. 1791 70

Heightened sensitivity of the diabetic proximal tubule to dietary salt leads to a paradoxical effect of salt on glomerular filtration rate (GFR) via tubuloglomerular feedback. Diabetic hyperfiltration is a feedback response to growth and hyperreabsorption by the proximal tubule. The present studies were performed to determine whether growth and hyperfunction of the proximal tubule are essential for its hyperresponsiveness to dietary salt and, hence, to the paradoxical effect of dietary salt on GFR. Micropuncture was performed in four groups of inactin-anesthetized Wistar rats after 10 days of streptozotocin diabetes drinking tap water or 1% NaCl. Kidney growth was suppressed with ornithine decarboxylase (ODC) inhibitor, DFMO (200 mg.kg(-1).day(-1)), or placebo. Single nephron GFR (SNGFR) was manipulated by perfusing Henle's loop so that proximal reabsorption (Jprox) could be expressed as a function of SNGFR in each nephron, dissociating primary effects on the tubule from the effects of glomerulotubular balance. Alone, DFMO or high salt reduced SNGFR and suppressed Jprox independent of SNGFR. Suppression of Jprox was eliminated and SNGFR increased when high salt was given to rats receiving DFMO. ODC is necessary for hyperresponsiveness of the proximal tubule to dietary salt and for the paradoxical effect of dietary salt on GFR in early diabetes. This coupling of effects adds to the body of evidence that feedback from the proximal tubule is the principal governor of glomerular filtration in early diabetes.
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PMID:Ornithine decarboxylase inhibitor eliminates hyperresponsiveness of the early diabetic proximal tubule to dietary salt. 1856 30

Reactive oxygen species have emerged as important molecules in cardiovascular dysfunction such as diabetes and hypertension. Recent work has shown that oxidative stress and angiotensin II signaling mutually regulate each other by multiple mechanisms and contribute to the development of hypertension. Most of the known biological actions of angiotensin II can be attributed to AT1 receptors. The present study was carried out to investigate the role of renal AT1 receptor signaling in oxidative stress-mediated hypertension. Male Sprague-Dawley rats received tap water (control) or 30 mM L-buthionine sulfoximine (BSO), an oxidant, with and without 1 mM tempol (an antioxidant) for 2 wk. Compared with control rats, BSO-treated rats exhibited increased oxidative stress and reduced antioxidant levels and developed hypertension. BSO treatment also caused increased renal proximal tubular AT1 receptor protein abundance, message levels, and ligand binding. In these rats, angiotensin II caused significantly higher accumulation of inositol trisphosphate (IP3) and phospholipase C (PLC) activation which was sensitive to blockade by AT1 but not to AT2 antagonist. Also, angiotensin II-mediated, AT1-dependent MAP kinase, Na-K-ATPase, and Na/H exchanger 3 activation was higher in BSO-treated rats than in control rats. Tempol supplementation of BSO-treated rats restored redox status, normalized AT1 receptor expression, and decreased blood pressure. Tempol also normalized the angiotensin II-mediated, AT1-dependent IP3 accumulation and PLC, MAP kinase, Na-K-ATPase, and Na/H exchanger 3 stimulation. These data suggest that oxidative stress leads to AT1 receptor upregulation, which in turn causes overstimulation of sodium transporters and subsequently contributes to sodium retention and hypertension. Tempol, while reducing oxidative stress, normalizes AT1 receptor signaling and decreases blood pressure.
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PMID:Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension. 1861 17

Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress, we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201+/-5 vs. 163+/-7 mm Hg in diabetic rats untreated and treated with lercanidipine, respectively; P<0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P<0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P<0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P<0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2/TIMP-2 expression.
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PMID:Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats. 1893 Jul 22

Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.
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PMID:Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. 1905 45

Recently, deep sea water (DSW) has started to receive much attention for therapeutic intervention in some lifestyle diseases. In this study, the anti-obesity and antidiabetic effects of DSW in ob/ob mice were investigated. The animals were randomly divided into two groups with six animals: control group received tap water; the experimental group was treated with DSW of hardness 1000 for 84 days. The body weight gain after 84 days in DSW-fed group was decreased by 7% compared to the control group. The plasma glucose levels in the DSW-fed mice were substantially reduced by 35.4%, as compared to control mice. The results of oral glucose tolerance test revealed that DSW-fed groups significantly increased the glucose disposal after 84 days. DSW increased plasma protein levels of adiponectin and decreased plasma protein levels of resistin, RBP4, and fatty acid binding protein. Moreover, GLUT4 and AMP-activated protein kinase levels in skeletal muscle tissue were increased while peroxisome proliferator-activated receptor gamma and adiponectin were decreased in adipose tissue of DSW-fed mice. These results suggest that the antidiabetic and anti-obesity activities of DSW were mediated by modulating the expression of diabetes- and obesity-specific molecules. Taken together, these results provide a possibility that continuous intake of DSW can ameliorate obesity and diabetes.
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PMID:Anti-obesity and antidiabetic effects of deep sea water on ob/ob mice. 1908 59

Obesity and related metabolic abnormalities, including insulin resistance, are risk factors for hepatocellular carcinoma in non-alcoholic steatohepatitis as well as in chronic viral hepatitis. Branched-chain amino acids (BCAA), which improve insulin resistance, inhibited obesity-related colon carcinogenesis in a rodent model, and also reduced the incidence of hepatocellular carcinoma in obese patients with liver cirrhosis. In the present study, we determined the effects of BCAA on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in obese C57BL/KsJ-db/db (db/db) mice with diabetes mellitus. Male db/db mice were given tap water containing 40 ppm DEN for an initial 2 weeks and thereafter they received a basal diet containing 3.0% of BCAA or casein, which served as a nitrogen content-matched control of BCAA, throughout the experiment. Supplementation with BCAA significantly reduced the total number of foci of cellular alteration, a premalignant lesion of the liver, and the expression of insulin-like growth factor (IGF)-1, IGF-2, and IGF-1 receptor in the liver when compared to the casein supplementation. BCAA supplementation for 34 weeks also significantly inhibited both the development of hepatocellular neoplasms and the proliferation of hepatocytes in comparison to the basal diet or casein-fed groups. Supplementation with BCAA improved liver steatosis and fibrosis and inhibited the expression of alpha-smooth muscle actin in the DEN-treated db/db mice. The serum levels of glucose and leptin decreased by dietary BCAA, whereas the value of the quantitative insulin sensitivity check index increased by this agent, indicating the improvement of insulin resistance and hyperleptinemia. In conclusion, oral BCAA supplementation improves insulin resistance and prevents the development of liver tumorigenesis in obese and diabetic mice.
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PMID:Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. 1990 67

Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de-endothelialization of the iliac arteries. Ballooned and age-matched control animals were assigned into subgroups receiving pomegranate extract antioxidants in drinking water or tap water as placebo. After 8 weeks, penile blood flow and erectile activity were recorded. Erectile tissue relaxation, oxidative products, oxidative stress-responsive genes and structure were examined using organ bath, enzyme immunoassay, quantitative real-time polymerase chain reaction and transmission electron microscopy, respectively. Arterial ballooning caused diffused atherosclerosis, decreased intracavernosal blood flow and led to ED. Impairment of endothelium-dependent relaxation, diffused fibrosis, increased oxidative products, upregulation of superoxide dismutase (SOD) and aldose reductase (AR) gene expression, mitochondrial and endothelial structural damage and increased caveolae were evident in erectile tissues from atherosclerotic animals receiving placebo. Upregulation of antioxidant enzymes SOD and AR failed to protect ischaemic erectile tissue from oxidative injury. Pomegranate extract significantly improved intracavernosal blood flow, erectile activity, smooth muscle relaxation and fibrosis of the atherosclerotic group in comparison with the atherosclerotic group receiving placebo, but did not normalize them to the age-matched control levels. Pomegranate extract appeared more effective in diminishing oxidative products, preventing SOD and AR gene upregulation, and protecting mitochondrial, endothelial and caveolae structural integrity of the atherosclerotic group. Our data suggest the presence of oxidative stress in ED and a more efficient action of antioxidants on molecular and ultrastructural alterations than on distinct functional deficit and structural damage in the ischaemic penis.
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PMID:Dietary antioxidants improve arteriogenic erectile dysfunction. 2058 92


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