Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to determine whether duodenum-preserving pancreatic head resections (DPPHRs) offer improved outcomes for benign disease of the proximal pancreas. A single-cohort study was performed of 86 consecutive patients who underwent DPPHR, extended lateral pancreaticojejunostomy with excavation of the pancreatic head (ELPJ), standard or pylorus-sparing Whipple procedure (WHIP), or distal pancreatectomy (DPR). Aspects of cost, complications (mortality and morbidity), and outcomes were assessed during a follow-up period of 6-63 months (mean, 3 years). Twelve DPPHR and 12 ELPJ procedures were performed for benign lesions or chronic pancreatitis (CP), as were 7 of 30 WHIP procedures and 12 of 16 DPRs. Operative time was significantly less than that for WHIP in ELPJ and DPR procedures. Major complications occurred in 40% of WHIPs and 25% of DPPHRs but only 16% of ELPJs (P < 0.05). Thirty-day mortality was 2 of 30 for WHIP but 0 for all other procedures. Pancreatic or biliary leak occurred in 3 of 30 WHIPs, 3 of 12 DPPHRs, 1 of 16 DPRs, and 0 of 12 ELPJs. New diabetes occurred in 25% of patients who underwent WHIP but only 8% of both DPPHR and ELPJ patients. Full functional recovery was similar for CP patients in both DPPHR and ELPJ. DPPHR and ELPJ are effective surgical approaches to the treatment of benign tumors and CP and are safer than WHIP with lower morbidity and mortality risks. The incidence of new diabetes is less with both ELPJ and DPPHR.
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PMID:Improved outcomes for benign disease with limited pancreatic head resection. 1574 4

Intracerebral hemorrhage (ICH) is a severe complication in diabetic patients. Currently, physical exercise is recommended as a behavioral intervention to promote functional recovery in brain diseases, including ICH. Recently, hyperglycemia is known to aggravate brain injury in experimental ICH. Here, we examined the effect of treadmill exercise on the intrastriatal hemorrhage-induced neuronal cell death and cell proliferation in the dentate gyrus of hyperglycemic rats. Hyperglycemia was induced by the intraperitoneal injection of 50 mg/kg streptozotocin (STZ). Intrastriatal hemorrhage was induced by the infusion of 0.2 U collagenase into the striatum using stereotaxic instrument. Rats in the exercise groups were forced to run on a treadmill for 30 min daily for 10 days. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Cell proliferation was assessed by the 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. Our data showed that in rats started treadmill exercise 24 h after ICH induction, the size of lesion induced by hemorrhage and the number of apoptotic cells were decreased significantly. The number of proliferating cells in the dentate gyrus was significantly decreased in hyperglycemic rats. Treadmill exercise markedly enhanced cell proliferation in the dentate gyrus of hyperglycemic rats. The data suggest that treadmill exercise may provide therapeutic value to ICH patients with hyperglycemia by suppressing neuronal apoptosis and increasing cell proliferation.
J Diabetes Complications
PMID:Early treadmill exercise decreases intrastriatal hemorrhage-induced neuronal cell death and increases cell proliferation in the dentate gyrus of streptozotocin-induced hyperglycemic rats. 1626 Mar 51

Increased hexosamine biosynthesis pathway (HBP) flux and elevated levels of protein O-linked-N-acetylglucosamine (O-GlcNAc) decrease calcium influx into isolated cardiomyocytes. Increased O-GlcNAc levels also increase tolerance of cells to stress. Therefore, the goal of this study was to test the hypothesis that increasing HBP flux and protein O-GlcNAc levels in the intact heart will increase the tolerance to tissue injury resulting from the calcium paradox and ischemia. We used two strategies that have been shown to increase HBP flux in the intact heart, namely a brief period of streptozotocin-induced diabetes and acute pretreatment of the isolated perfused heart with glucosamine. Isolated perfused rat hearts were exposed to the calcium paradox or to ischemia and reperfusion. Both diabetes and glucosamine significantly improved recovery in the isolated perfused rat heart following the calcium paradox with left ventricular developed pressure (LVDP) returning to ~80% of baseline compared to 0% in controls (P<0.05), and lactate dehydrogenase release being reduced by approximately fivefold (P<0.05). In the diabetic group, azaserine, which inhibits the HBP, restored the sensitivity to the calcium paradox. Glucosamine treatment also improved functional recovery following ischemia/reperfusion (LVDP: 47+/-9% vs. 95+/-4%, P<0.05) and this was associated with a threefold increase in O-GlcNAc levels (P<0.05). Alloxan, an inhibitor of O-GlcNAc-transferase, blocked both the protection seen with glucosamine and the increase in O-GlcNAc. These data demonstrate that activation of the HBP with glucosamine may be a novel strategy for inducing cardioprotection, and that this appears to be mediated by an increase in protein O-GlcNAc levels.
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PMID:Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia. 1633 59

Stroke is the third leading cause of death in the United States after heart disease and cancer; it has an incidence of approximately 750,000 cases per year, and it is a leading cause of disability in adults. The factors predicting a poor outcome from stroke include severe initial neurological dysfunction, hypertension, cardiac arrhythmias, myocardial infarction, hypercholesterolemia, and diabetes mellitus. The armamentarium available for improvement of neurological function after stroke is currently limited to placement in specialized stroke units, optimal therapy for medical complications, and intense physical, occupational and speech rehabilitation. Despite many trials, no pharmacological intervention has been shown convincingly to improve neurological outcome. This review was undertaken to determine the appropriate time for new approaches to the therapy of stroke such as the infusion of stem cells into the central nervous system. The literature shows in large case series that functional recovery from stroke reaches a maximum level by 3-6 months after onset, and no further recovery occurs beyond this time. Nevertheless, about 80% of these patients reach their maximum function for activities of daily living within 6 weeks from onset. Initiation of a clinical trial of stem cell therapy would require demonstration of optimal clinical improvement by neurological evaluations, with no change over at least 4 weeks of observation. Accordingly, in subjects with first-ever ischemic stroke who remained neurologically unchanged from the second until the third month after the acute event, implementation of stem cell therapy would be appropriate at approximately 3 months after the stroke.
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PMID:Time course and outcome of recovery from stroke: relevance to stem cell treatment. 1642 47

Previous studies have shown that intracavernous injection of vascular endothelial growth factor (VEGF) restored erectile function in diabetic rats. However, the mechanism of VEGF in diabetes-related erectile dysfunction (ED) has not been fully investigated. We hypothesize that intracavernous injection of VEGF may reverse diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To test this hypothesis the erectile function of treated and control rats was analyzed by measurement of intracavernous pressure (ICP) following electrostimulation of the cavernous nerves. Mean ICP was significantly lower in non-treated diabetic rats compared to controls. After VEGF injection, ICP was significantly higher than in non-treated diabetic rats. IGFBP-3 mRNA and protein expression was significantly higher in non-treated diabetic rat crura than controls, while VEGF-treated animals had control levels. ER-beta and PR mRNA and protein expression was significantly lower in non-treated diabetic rat crura. After VEGF injection, ER-beta and PR mRNA and protein expression was similar to control levels. Expression of AR and ER-alpha was the same in all groups. These findings suggest that orthotopic injection of VEGF may improve the functional recovery of diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To our knowledge, this is the first study demonstrating that VEGF treatment restores erectile function through restoration of the insulin-like growth factor system and sex hormone receptor genes at the mRNA and protein levels in diabetic rat crura. These results may be important in understanding the pathogenesis of diabetes-related ED and also in providing better strategies for management of this disease.
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PMID:Vascular endothelial growth factor restores erectile function through modulation of the insulin-like growth factor system and sex hormone receptors in diabetic rat. 1645 52

We studied clinical characteristics and prognosis in acute stoke patients with diabetes mellitus registered on the Japanese Standard Stroke Registry database. A total of 16,630 acute stroke patients admitted to 56 hospitals in Japan. They were examined as to their stroke types, risk factors, their severity of stroke according to the NIH Stroke Scale (NIHSS) and Japan Stroke Scale (JSS), and outcomes by the modified Rankin Scale (m-RS). The incidence of subarachnoid hemorrhage was relatively high in the group of patients who had neither hypertension nor diabetes, and the incidence of brain hemorrhage was higher in the group of patients who had hypertension without diabetes. The frequencies of lacunar infarct and atherothrombotic infarct were also higher in the group of patients who had both hypertension and diabetes. In the diabetic group without hypertension, there were less numbers of hemorrhagic stroke. The ratio of good prognosis (m-RS 0-1) was significantly smaller in the diabetic patients with lacunar infarction, cardioembolic infarction, and subarachnoid hemorrhage. Additionally, there was significantly more stroke recurrence in the diabetic patients (33.0% vs. 26.9%, p<0.0001). The diabetic patients who received insulin therapy (-0.8 +/- 7.4), diet therapy (-0.4 +/- 9.4), or oral medicine (-0.9 +/- 7.2), showed significantly less improvements in the NIHSS compared to the non-diabetic patients (-1.6 +/- 8.2), respectively. Moreover, the poor-management diabetic patients showed significantly less improvements in the JSS compared to non diabetic patients (3.8 +/- 7.7 vs. 4.8 +/- 8.6, p<0.005). In conclusions, stroke patients with diabetes mellitus showed more stroke recurrence and resulted in poorer functional recovery compared to patients without diabetes.
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PMID:[Clinical characteristics and prognosis in stroke patients with diabetes mellitus: retrospective evaluation using the Japanese Standard Stroke Registry database (JSSRS)]. 1651 9

High fructose-fed (HFF) rat model is known to develop the insulin-resistant syndrome with a very similar metabolic profile to the human X syndrome. Such metabolic modifications have been associated with a high incidence of cardiovascular disease. The role of free radical attack in diabetes mellitus and its cardiovascular complications have been abundantly documented. The present study examined the susceptibility to myocardial ischemic injury and the involvement of free radical attack and/or protection in the metabolic disorders of high FF rats. Rats were divided into two experimental groups that received diet for 4 weeks: a control group (C, n=28) receiving a standard diet and a HFF group (FF, n=28), in which 58% of the total carbohydrate was fructose. The euglycemic clamp technique was performed to assess insulin resistance. For the ischemia-reperfusion procedure, rat hearts were isolated and perfused at constant pressure before they were subjected to a 30-min occlusion of the left coronary artery followed by 120 mins of reperfusion. Hemodynamic parameters were measured throughout the protocol. Infarct-to-risk ratio (I/R) was assessed at the end of the protocol by 2,3,4-triphenyltetrazolium chloride staining and planimetric analysis. Lipid peroxidation, antioxidant enzyme activity, level of vitamin E, and trace element status were measured in blood samples from both groups. Rats of the FF group developed an insulin resistance indicated by the glucose infusion rate, which was decreased by 47%. Infarct size was significantly reduced in rats from the FF group (19.9% +/- 6.6%) compared to rats from the control group (34.6% +/- 4.9%), and cardiac functional recovery at reperfusion was improved in the FF group. Lipid peroxidation and oxidative stress were higher in the FF group, as indicated by higher malonedialdehyde level, whereas plasma vitamin E/triacylglycerol ratio was also enhanced in this group. This study indicates that fructose feeding affords protection against in vitro ischemia-reperfusion injury, potentially implicating vitamin E.
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PMID:Fructose-fed rat hearts are protected against ischemia-reperfusion injury. 1656 41

We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. STZ-induced male diabetic rats were treated with insulin (STZ-insulin group, n = 26) or vehicle (STZ-vehicle group, n = 61) for 3 weeks. Whole-body hyperthermia (43 degrees C for 20 min) was applied, and the heart was isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart. Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia-treated STZ-vehicle heart showed poor left ventricular functional recovery during reperfusion after no-flow global ischemia compared with hyperthermia-treated control heart. Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. In cultured neonatal rat cardiomyocytes, hyperthermia-induced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency.
Diabetes 2006 May
PMID:Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart. 1664 87

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, not only improves insulin resistance in patients with type II diabetes but also exerts a broad spectrum protective effects in variable animal models of neurologic or cardiovascular diseases. We studied the effect of rosiglitazone on angiogenesis and neurological recovery after focal cerebral ischemia. Rosiglitazone (3 mg/kg or 0.3 mg/kg, p.o.) was administered for 7 days prior to and 3 days after the induction of focal ischemia (total 10 days) in adult rats. The rosiglitazone-treated group showed the enhanced neurologic improvement, the reduced infarction volume compared to the ischemia-vehicle group with dose dependency, and the reduced hemispheric atrophy. Rosiglitazone treatment reduced TUNEL(+)/activated caspase-3(+) cells, MPO(+)/Ox-42(+) inflammatory cell infiltrations, caspase-3 activity, and Bax(+) cells, as compared to the ischemia-vehicle group. The vascular surface area, the vascular branch points, the vascular length, and the number of BrdU(+) endothelial cells were significantly increased in the rosiglitazone group compared with the ischemia-vehicle group. Rosiglitazone increased eNOS expression around the ischemic margin with downregulation of FasL. Here, we show that rosiglitazone treatment enhances angiogenesis and functional recovery with dose-dependent induction of ischemic tolerance.
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PMID:Peroxisome proliferator-activated receptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia. 1669 56

Diabetes mellitus is a degenerative disease that has deleterious effects on male reproductive function, possibly through an increase in oxidative stress. This study was conducted in order to clarify the mechanisms by which oxidative stress influences animal models for both type 1 (streptozotocin-treated rats, STZ) and type 2 (Goto-Kakizaki (GK) rats) diabetes. We determined the extent of lipid peroxidation, protein oxidation, lactate levels, adenine nucleotides, adenylate energy charge and the activity of glutathione peroxidase, glutathione reductase and lactate dehydrogenase, in isolated testicular cells of control and diabetic rats. We have also correlated these parameters with sperm count and motility. Sperm concentration and motility were decreased in STZ-treated rats. ATP levels were lower in rats treated with STZ for 3 months, in contrast to GK and rats treated with STZ for 1 month, suggesting an adaptative response. STZ-treated rats showed increased lipid peroxidation after 1 week and 3 months of treatment. Glutathione reductase (G-red) activity was found to be higher in GK rats. Glutathione peroxidase activity was lower in GK and rats treated with STZ for 1 month, which is in accordance with the proposal of functional recovery in these animals. We conclude that hyperglycemia has an adverse effect in sperm concentration and motility via changes in energy production and free radical management. Furthermore, both animal models, particularly GK rats and rats treated with STZ for 1 month, present some metabolic adaptations, increasing the efficiency of mitochondrial ATP production, in order to circumvent the deleterious effects promoted by the disease.
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PMID:Effects of hyperglycemia on sperm and testicular cells of Goto-Kakizaki and streptozotocin-treated rat models for diabetes. 1686 Mar 81


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