UMLS:C0011849 - FACTA Search

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

The chronic hyperglycaemia associated with diabetes mellitus increases susceptibility to epileptiform-like activity in the central nervous system. Changes in extracellular potassium levels directly influence neuronal excitability and significantly one of the major regulators of extracellular potassium, the Na-K ATPase, is known to be down-regulated by chronic hyperglycaemia. The sensitivity of hippocampal slices, from rats made diabetic for 2-3 weeks with streptozotocin, to increases in the extracellular potassium concentration ([K+]o) was, therefore, investigated. Raising [K+]o to 10 mM increased the number of orthodromically-evoked population spikes (PSs) in area CA1. This recruitment was significantly greater in hippocampal slices from diabetic rats, which also exhibited significantly more spontaneous activity. These findings confirm a diabetes-dependent increase in sensitivity of central neurones to changes in [K+]o and may help to explain the increased susceptibility to epileptiform activity in this disease state.
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PMID:Chronic hyperglycaemia increases neuronal sensitivity to high potassium in hippocampal slices from streptozotocin-treated diabetic rats. 1067 32

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.
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PMID:Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis. 1082 93

Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron deficient group (p < 0.001). Areas with significantly reduced CytOx activity (p < 0.001) included all measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not involved in higher cognitive functions, did not have significantly reduced CytOx activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron deficiency differentially reduces neuronal metabolic activity, specifically targeting areas of the brain involved in memory processing.
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PMID:Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain. 1092 85

Wolfram (DIDMOAD) syndrome is an autosomal recessive neurodegenerative disorder accompanied by insulin-dependent diabetes mellitus and progressive optic atrophy. Recent positional cloning led to identification of the WFS1 (Wolfram syndrome 1) gene, a member of a novel gene family of unknown function. In this study, we generated a specific antibody against the C-terminus of the WFS1 protein and investigated its subcellular localization in cultured cells. We also studied its distribution in the rat brain. Biochemical studies indicated the WFS1 protein to be an integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). Consistent with this, immunofluorescence cell staining of overexpressed WFS1 showed a characteristic reticular pattern over the cytoplasm and overlapped with the ER marker staining. No co-localization of WFS1 with mitochondria argues against an earlier clinical hypothesis that Wolfram syndrome is a mitochondria-mediated disorder. In the rat brain, at both the protein and mRNA level, WFS1 was found to be present predominantly in selected neurons in the hippocampus CA1, amygdaloid areas, olfactory tubercle and superficial layer of the allocortex. These expression sites, i.e. components of the limbic system or structures closely associated with this system, may be involved in the psychiatric, behavioral and emotional abnormalities characteristic of this syndrome. ER localization of WFS1 suggests that this protein plays an as yet undefined role in membrane trafficking, protein processing and/or regulation of ER calcium homeostasis. These studies represent a first step toward the characterization of WFS1 protein, which presumably functions to maintain certain populations of neuronal and endocrine cells.
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PMID:WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. 1118 71

Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants--coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme--caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment.
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PMID:Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. 1177 Jan 25

We recorded the effects of hypoxia combined with relative hypoglycemia on pre- and post-synaptic potentials in the CA1 area of slices from 4-month-old control and diabetic (streptozotocin-treated) Wistar rats. In experiments on slices kept in 10 or 4 mM glucose (at 33 degrees C), hypoxia was applied until the pre-synaptic afferent volley disappeared--after 12-13 min in most slices, but much earlier (5+/-0.8 min) in diabetic slices kept in 4 mM glucose. When oxygenation was resumed, the afferent volley returned in all slices, for an overall mean recovery of 86.5% (+/-8.8%). Field post-synaptic potentials were fully blocked within 2-3 min of the onset of hypoxia. After the end of hypoxia, they failed to reappear in some slices: overall, their recovery varied between 62 and 68% in control slices, as well as in diabetic slices kept in 10 mM glucose; but recovery was very poor in diabetic slices kept in 4 mM glucose (only 15+/-0.94%). In the latter, hypoxic injury discharges occurred earlier (4.2+/-0.68 min vs. 6.5-8 min for other groups). We conclude that diabetes appears to make hippocampal slices more prone to irreversible loss of synaptic function and early block of axonal conduction when temporary hypoxia is combined with moderate hypoglycemia.
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PMID:Moderate hypoglycemia aggravates effects of hypoxia in hippocampal slices from diabetic rats. 1212 80

In streptozotocin-induced diabetic (STZ-diabetic) rats, an animal model of diabetes mellitus, a reduced expression of long-term potentiation (LTP) and enhanced long-term depression (LTD) are observed. This study examined the role of protein kinase C (PKC) and protein phosphatase 2B in hippocampal synaptic transmission in STZ-diabetic rats. The phorbol ester 4beta-phorbol-12,13-dibutyrate (PDB) induced a concentration-dependent potentiation of synaptic responses in area CA1 that could partially be inhibited by the PKC inhibitor chelerythrine. In slices from STZ-diabetic rats the effectivity of PDB to increase synaptic transmission was reduced compared to slices from control animals. In STZ-diabetic rats the protein phosphatase 2B (PP2B) inhibitor cyclosporin A inhibited LTD induction, but did not affect the induction of LTP. In conclusion, these data show a reduced response to PDB in STZ-diabetic rats, and indicate that the lack of LTP induction in these animals is not due to increased PP2B activity.
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PMID:Effects of a phorbol ester and cyclosporin A on hippocampal synaptic plasticity in streptozotocin-induced-diabetic rats: reduced sensitivity to phorbol esters. 1261 97

Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca(2+) spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca(2+) influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging.
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PMID:Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats. 1269 92

Oxidative stress has been implicated in the pathophysiology of Alzheimer's disease (AD) and diabetes mellitus (DM). N epsilon-carboxymethyllysine (CML) is an advanced glycation end product (AGE) recently found to be associated with oxidative stress mechanisms. Using immunocytochemical methods we examined the distribution of CML in brain tissue from AD and DM subjects and aging controls. CML reactivity was present in the cytoplasm of neurons, but there were marked differences in the intensity of expression, number of cells, and topographical distribution. CML expression was higher in hippocampus than in frontal and temporal cortex. In the hippocampus, neuronal and, to an extent, glial expression was more marked in CA3 and CA4 than in CA1 and CA2. In AD, CML was found to be coexpressed with tau protein, showing the similar neurofibrillary tangle shape, as well as in neuritic plaques but not in the core of amyloid plaques. We noted an increasing degree of CML expression such that the highest reactivity was evident in those with both AD and DM, followed by AD, DM, and aging controls. There was an inverse relationship between Braak staging and topography of CML expression. Although DM cases did not show Abeta deposition or neurofibrillary tangles, these findings suggest increased CML expression is not limited to AD. Nonetheless, high CML expression in AD with coexistent DM suggests there are additive effects compared with AD alone. It is plausible that the microangiopathy also associated with DM could worsen AD pathogenesis.
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PMID:N epsilon-carboxymethyllysine in brain aging, diabetes mellitus, and Alzheimer's disease. 1511 Mar 89

The influence of hypertension associated with diabetes on cerebrovascular and frontal cortex or hippocampus microanatomy was investigated in 20-week-old spontaneously hypertensive rats (SHR) in which diabetes was induced by treatment with streptozotocin (STZ) and in control or STZ-diabetic age-matched normotensive Wistar Kyoto (WKY) rats. At the beginning of experiment, systolic pressure values were similar in WKY rats either control, or exposed to STZ and remarkably higher in control or STZ-treated SHR. Systolic pressure values increased in the different animal groups examined along the course of experiment. Blood glucose levels were increased in either STZ-WKY rats or -SHR compared to WKY rats and SHR respectively. The main changes occurring in pial and intracerebral arteries of SHR and STZ-SHR were thickening of the arterial wall accompanied by luminal narrowing. In medium sized pial arteries of STZ-WKY rats luminal narrowing and a decreased thickness of arterial wall were noticeable. Intracerebral arteries of STZ-WKY diabetic rats showed a not homogeneous sensitivity of different sized branches. The volume of zones III and IV of frontal cortex was decreased in SHR and STZ-SHR compared to control WKY rats. The number of nerve cells in these cerebrocortical layers was decreased to a similar extent in SHR. STZ-WKY rats or STZ-SHR compared to control WKY rats. In dentate gyrus, followed by the CA1 subfield of hippocampus, decreased volume and number of neurons were found in SHR and STZ-SHR compared to control WKY rats. The occurrence of astrogliosis was observed in hypertensive, diabetic or hypertensive plus diabetic rats. The above findings indicate the occurrence of cerebrovascular and brain microanatomical changes in SHR and to a lesser extent in STZ-diabetic rats compared to control normotensive and normoglicemic WKY rats. Association of hypertension and diabetes caused more pronounced changes than in the single disease models. These results support the view that hypertension and diabetes affect the structure of cerebrovascular tree and of brain and that association of the two diseases results in an increased risk of target-organ damage, involving brain.
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PMID:Cerebrovascular and brain microanatomy in spontaneously hypertensive rats with streptozotocin-induced diabetes. 1519 86

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