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

The synaptophysin (Syn) and neuropeptide Y (NPY) expressions in brain tissue of diabetic model rats were investigated. 20 adult Sprague-Dawley male rats were randomly divided into two groups. 10 rats were injected with streptozotocin to induce diabetes, which was identified by blood & urinary sugar level; and the others were injected with sodium citrate buffer as the control. After 4 weeks' diabetes appearance, the learning and memory ability of each rat in both group were tested by Y-Maze. Afterward freeze sections from the frontal cortex and hippocampus were made and stained with Nissl and Syn, NPY Immunohistochemistry staining. It was observed that diabetic rats showed more errors in Y-Maze test than those control rats. Both the number of neurons and the light densities of Syn and NPY immunostaining reaction in the frontal cortex and hippocampus of brain tissue sections significantly decreased in the diabetic model rats. It is suggested that the decrease in neuron number and Syn, NPY expression in frontal cortex and hippocampus may be one of the factors leading to diabetic dementia.
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PMID:[The investigation of Syn and NPY expression in brain tissues of diabetic model rat induced by streptozotocin]. 1578 63

Amyloid-containing (A+) islets are characteristic for type-2 diabetes (T2D), but their abundance seems variable among patients. It is unclear whether the distribution of A+ islets follows a certain pattern or occurs randomly throughout the pancreatic organ. We investigated the topography of A+ islets in eight pancreata of T2D patients and eight sex- and age-matched non-diabetic subjects. Transversal sections of head, body and tail segments were stained with synaptophysin combined with Congo red to map/quantify islet tissue and amyloid. In the eight T2D pancreata, the overall percentage of A+ islets varied from 4% to 85%. Further analysis in body and tail indicated that peripheral regions exhibited higher percentages of A+ islets than central regions (averages of, respectively, 30% and 17%, P<0.05). Non-diabetic control pancreata also exhibited A+ islets, albeit at a 25-fold lower frequency; a tendency towards higher percentage of A+ islets in peripheral versus central regions was also observed. The higher percentage A+ islets in peripheral regions was associated with a higher density and relative islet over exocrine surface area. These observations on heterogeneity in abundance and distribution of A+ islets need consideration when sampling tissue for studies on human islet amyloidosis. The present methodology allows us to further investigate the susceptibility to amyloidosis of islets in peripheral regions of the pancreas.
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PMID:Heterogeneity in distribution of amyloid-positive islets in type-2 diabetic patients. 1579 82

The hippocampus, an important integration center for learning and memory in the mammalian brain, undergoes neurological changes in response to a variety of stimuli that are suggestive of ongoing synaptic reorganization. Accordingly, the aim of this study was to identify markers of synaptic plasticity using rapid and reliable techniques such as radioimmunocytochemistry and confocal microscopy, thereby providing a "birds-eye view" of the whole hippocampus under hypercorticosteronemic conditions. The regulation of microtubule-associated protein 2, synaptophysin and postsynaptic density-95 was examined in two different animal models of hypercorticosteronemia: corticosterone administration and streptozotocin-induced diabetes using both a short-term (1 week) and long-term (5 weeks) treatment. Glucocorticoids and/or hyperglycemia increased synaptophysin expression in CA1, CA3 and the dentate gyrus, regions that exhibit synaptic plasticity in response to glucocorticoid exposure. In these models, postsynaptic density-95 expression increased in the CA3 region, particularly in the diabetic rats, while microtubule-associated protein 2 exhibited more selective changes. Fluoro-Jade histochemistry did not detect neuronal damage, suggesting that glucocorticoids and/or hyperglycemia induce plastic and not irreversible neuronal changes at these time points. Collectively, these results demonstrate that changes in the expression and distribution of synaptic proteins provide another measure of synaptic plasticity in the rat hippocampus in response to glucocorticoid exposure, changes that may accompany or contribute to neuroanatomical, neurochemical, and behavioral changes observed in experimental models of type 1 diabetes.
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PMID:Immunocytochemical analysis of synaptic proteins provides new insights into diabetes-mediated plasticity in the rat hippocampus. 1622 81

Exocytosis of insulin is dependent on the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins in the B-cells. We assessed insulin release as well as gene and protein expression of SNARE complex protein in isolated pancreatic islets of type 2 diabetic patients (n = 4) and nondiabetic control subjects (n = 4). In islets from the diabetic patients, insulin responses to 8.3 and 16.7 mmol/l glucose were markedly reduced compared with control islets (4.7 +/- 0.3 and 8.4 +/- 1.8 vs. 17.5 +/- 0.1 and 24.3 +/- 1.2 microU . islet(-1) . h(-1), respectively; P < 0.001). Western blot analysis revealed decreased amounts of islet SNARE complex and SNARE-modulating proteins in diabetes: syntaxin-1A (21 +/- 5% of control levels), SNAP-25 (12 +/- 4%), VAMP-2 (7 +/- 4%), nSec1 (Munc 18; 34 +/- 13%), Munc 13-1 (27 +/- 4%), and synaptophysin (64 +/- 7%). Microarray gene chip analysis, confirmed by quantitative PCR, showed that gene expression was decreased in diabetes islets: syntaxin-1A (27 +/- 2% of control levels), SNAP-25 (31 +/- 7%), VAMP-2 (18 +/- 3%), nSec1 (27 +/- 5%), synaptotagmin V (24 +/- 2%), and synaptophysin (12 +/- 2%). In conclusion, these data support the view that decreased islet RNA and protein expression of SNARE and SNARE-modulating proteins plays a role in impaired insulin secretion in type 2 diabetic patients. It remains unclear, however, to which extent this defect is primary or secondary to, e.g., glucotoxicity.
Diabetes 2006 Feb
PMID:Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. 1644 78

Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested the hypothesis that diabetes decreases the retinal expression of presynaptic proteins involved in synaptic function. The protein and mRNA contents for synapsin I, synaptophysin, vesicle-associated membrane protein 2, synaptosomal-associated protein of 25 kDa and postsynaptic density protein of 95 kDa were measured by immunohistochemistry, immunoblotting and real-time quantitative polymerase chain reaction in whole retinas and retinal synaptosomes from streptozotocin-diabetic and control Sprague-Dawley rats. There was less presynaptic protein immunoreactivity after 1 and 3 months of diabetes than in controls. Discrete synaptophysin-immunoreactive puncta were significantly smaller and fewer in sections from 1- and 3-month diabetic rat retinas than in those from controls. The content of presynaptic proteins was significantly less in whole retinas of 1- and 3-month diabetic rats, and in synaptosomes from 1-month diabetic rats, than in controls. Whole retinas had significantly less mRNA for these genes after 3 months but not 1 month of diabetes, as compared to controls (with the exception of postsynaptic density protein of 95 kDa). In contrast, there was significantly less mRNA for synaptic proteins in synaptosomes of 1-month diabetic rats than in controls, suggesting a localized depletion at synapses. Protein and mRNA for beta-actin and neuron-specific enolase were unchanged by diabetes. The ratio of phosphorylated to total synapsin I was also reduced in whole retina and isolated synaptosomes from 1-month diabetic rats, as compared to controls. These data suggest that diabetes has a profound impact on presynaptic protein expression in the retina, and may provide a mechanism for the well-established defects in vision and the electrophysiological response of the retina in diabetes.
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PMID:Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina. 1866 30

A limiting factor to the clinical management of diabetes is iatrogenic hypoglycemia. With multiple hypoglycemic episodes, the collective neuroendocrine response that restores euglycemia is impaired. In our animal model of recurrent hypoglycemia (RH), neuroendocrine deficits are accompanied by a decrease in medial hypothalamic activation. Here we tested the hypothesis that the medial hypothalamus may exhibit unique changes in the expression of regulatory proteins in response to RH. We report that expression of the immediate early gene FosB is increased in medial hypothalamic nuclei, anterior hypothalamus, and posterior paraventricular nucleus of the thalamus (THPVN) of the thalamus following RH. We identified the hypothalamic PVN, a key autonomic output site, among the regions expressing FosB. To identify the subtype(s) of neuronal populations that express FosB, we screened candidate neuropeptides of the PVN for coexpression using dual fluorescence immunohistochemistry. Among the neuropeptides analyzed [including oxytocin, vasopressin, thyrotropin-releasing hormone, and corticotropin-releasing factor (CRF)], FosB was only identified in CRF-positive neurons. Inhibitory gamma-aminobutyric acid-positive processes appear to impinge on these FosB-expressing neurons. Finally, we observed a significant decrease in the presynaptic marker synaptophysin within the PVN of RH-treated vs. saline-treated rats, suggesting that rapid alterations of synaptic morphology may occur in association with RH. Collectively, these data suggest that RH stress triggers cellular changes that support synaptic plasticity, in specific neuroanatomical sites, which may contribute to the development of hypoglycemia-associated autonomic failure.
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PMID:Recurrent hypoglycemia alters hypothalamic expression of the regulatory proteins FosB and synaptophysin. 1875 63

Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential adverse systemic effects. Daily I-I, subcutaneous insulin (S-I) or placebo in separate cohorts of diabetic and non-diabetic CD1 mice were delivered over 8 months of life. Radio-labelled insulin delivery revealed that I-I delivered more rapid and substantial insulin levels within the cerebrum with less systemic insulin detection when compared with S-I. I-I delivery slowed development of cognitive decline within weekly cognitive/behavioural testing, ameliorated monthly magnetic resonance imaging abnormalities, prevented quantitative morphological abnormalities in cerebrum, improved mouse mortality and reversed diabetes-mediated declines in mRNA and protein for phosphoinositide 3-kinase (PI3K)/Akt and for protein levels of the transcription factors cyclic AMP response element binding protein (CREB) and glycogen synthase kinase 3beta (GSK-3beta) within different cerebral regions. Although the murine diabetic brain was not subject to cellular loss, a diabetes-mediated loss of protein and mRNA for the synaptic elements synaptophysin and choline acetyltransferase was prevented with I-I delivery. As a mechanism of delivery, I-I accesses the brain readily and slows the development of diabetes-induced brain changes as compared to S-I delivery. This therapy and delivery mode, available in humans, may be of clinical utility for the prevention of pathological changes in the diabetic human brain.
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PMID:Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. 2486 Jan 27

Type 1 diabetes can affect hippocampal function triggering cognitive impairment through unknown mechanisms. Caffeine consumption prevents hippocampal degeneration and memory dysfunction upon different insults and is also known to affect peripheral glucose metabolism. Thus we now characterized glucose transport and the neurochemical profile in the hippocampus of streptozotocin-induced diabetic rats using in vivo(1)H NMR spectroscopy and tested the effect of caffeine consumption thereupon. We found that hippocampal glucose content and transport were unaltered in diabetic rats, irrespective of caffeine consumption. However diabetic rats displayed alterations in their hippocampal neurochemical profile, which were normalized upon restoration of normoglycaemia, with the exception of myo-inositol that remained increased (36 +/- 5%, p < 0.01 compared to controls) likely reflecting osmolarity deregulation. Compared to controls, caffeine-consuming diabetic rats displayed increased hippocampal levels of myo-inositol (15 +/- 5%, p < 0.05) and taurine (23 +/- 4%, p < 0.01), supporting the ability of caffeine to control osmoregulation. Compared to controls, the hippocampus of diabetic rats displayed a reduced density of synaptic proteins syntaxin, synaptophysin and synaptosome-associated protein of 25 kDa (in average 18 +/- 1%, p < 0.05) as well increased glial fibrillary acidic protein (20 +/- 5%, p < 0.05), suggesting synaptic degeneration and astrogliosis, which were prevented by caffeine consumption. In conclusion, neurochemical alterations in the hippocampus of diabetic rats are not related to defects of glucose transport but likely reflect osmoregulatory adaptations caused by hyperglycemia. Furthermore, caffeine consumption affected this neurochemical adaptation to high glucose levels, which may contribute to its potential neuroprotective effects, namely preventing synaptic degeneration and astrogliosis.
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PMID:Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. 1969 1

Recent work suggests that diabetes affects processing of peripheral, spinal and supraspinal signals in the spinal cord. However, there is little evidence for spinal cord lesions that would account for alterations in behavioral responses induced by experimental diabetes. Therefore, we assessed the expression of proteins that might affect neuronal cytoskeletal stability and thus promote dendritic and synaptic reorganization in diabetic rats. Expression of ILK, PINCH, PI3K, GSK-3beta, tau, MAP2, synaptophysin and drebrin in the lumbar spinal cord of non-diabetic and streptozotocin-diabetic rats was assessed by Western-blot analysis and immunocytochemistry after 8 and 20weeks of diabetes. The impact of diabetes on the proteins studied was duration-dependent with changes observed after 20 but not 8weeks of diabetes. ILK and PINCH proteins levels were significantly decreased and both colocalized to neurons and oligodendrocytes. PI3K protein levels were also significantly decreased, while GSK-3beta activity tended to be increased. Phosphorylation of tau and MAP2A/B protein expression were significantly increased, and expression of synaptophysin and drebrin were reduced in diabetic rats. Decreased ILK and PINCH as well as alterations of components of related signaling pathways are associated with tau hyperphosphorylation, MAP2 overexpression and reduction of synaptic proteins in the spinal cord of diabetic rats, suggesting that ILK and PINCH contribute to stabilization of axonal and dendritic structures. However, these changes are not likely the cause of altered behavioral responses in diabetic rats that occur after short-term diabetes, but may contribute to structural changes occurring in long-term diabetes.
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PMID:Diabetes induces changes in ILK, PINCH and components of related pathways in the spinal cord of rats. 2034 24

This study investigated whether exacerbation of poststroke dementia by diabetes associated abnormal tau phosphorylation and its mechanism. Streptozotocin (STZ) injection and/or a high fat diet (HFD) were used to treat rats to induce type 1 and 2 diabetes. Animals were randomly divided into STZ, HFD, STZ-HFD, and normal diet (NPD) groups. Focal ischemic stroke was induced by middle cerebral artery occlusion (MCAO). Cognitive function was tested by the Morris water maze. STZ or STZ-HFD treatment exacerbated ischemia-induced cognitive deficits, brain infarction and reduction of synaptophysin expression. Moreover, we found that diabetes further increased AT8, a marker of hyperphosphorylated tau, protein and immunopositive stained cells in the hippocampus of rats following MCAO while reduced the level of phosphorylated glycogen synthase kinase 3-beta at serine-9 residues (p-ser9-GSK-3beta), indicating activation of GSK-3beta. We conclude that diabetes further deteriorates ischemia-induced brain damage and cognitive deficits which may be associated with abnormal phosphorylation of tau as well as activation of GSK-3beta. These findings may be helpful for developing new strategies to prevent/delay formation of poststroke dementia in patients with diabetes.
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PMID:Diabetes synergistically exacerbates poststroke dementia and tau abnormality in brain. 2039 14


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