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

1. Hippocampal slices have been used to assess the sensitivity of the CNS to adenosine and gamma-aminobutyric acid (GABA) in diabetes. The effects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen were studied on orthodromic synaptic potentials recorded in the CA1 region of slices taken from normal rats or animals made diabetic by the injection of streptozotocin. 2. In diabetic animals the sensitivity to adenosine was increased 4 fold compared with normal rats. The potency of 2-chloroadenosine was unchanged. 3. The nucleoside transport inhibitor, hydroxynitrobenzylthioinosine (HNBTI), increased the potency of adenosine in slices from normal rats but not in slices from diabetic rats. 4. No change was observed in the potency of GABA or muscimol, although a small but significant decrease was detected in the EC50 value for baclofen. 5. Treatment of diabetic animals with insulin restored the potency of adenosine to control levels. 6. It is concluded that the diabetic state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemical changes following from this in human diabetic patients may contribute to the reported behavioural changes.
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PMID:Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin-induced diabetes. 150 9

Glycosylated form of carbonic anhydrase isozyme I was found in human erythrocytes. The percent of glycosylated enzyme of the total erythrocyte carbonic anhydrase I of patients with diabetes mellitus was significantly higher than that from normal controls. Characterization of the glycosylated carbonic anhydrase I was studied using an enzyme purified from diabetic patients. The glycosylated enzyme showed a slightly acidic isoelectric point in comparison with that of a nonglycosylated enzyme. The specific activity of the glycosylated enzyme was approximately 40% of that of the normal enzyme, and the immunological activity decreased to 52% of that of the normal enzyme. Estimation of carbohydrates which may form a ketoamine linkage with the enzyme was studied using [3H]-labelled glycosylated enzyme synthesized by incubation of the enzyme with [3H]-D-glucose in vitro, and it was found that one mol of glucose binds to one mol of enzyme. Exposure of red cells to a higher concentration of glucose in diabetics brought about glycosylation of carbonic anhydrase, which is associated with its low activity enzymatically and immunologically.
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PMID:Estimation and characterization of glycosylated carbonic anhydrase I in erythrocytes from patients with diabetes mellitus. 311 73

Glucagon-like polypeptides, GLP-1-(7-36)-amide and GLP-1-(7-37), are important regulators of insulin synthesis and secretion by islet beta-cells. The hypothesis to be tested in this study was that defects in the islet beta-cell GLP-1 receptor gene contribute to the impaired glucose-regulated insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM). Human islet GLP-1 receptor genomic clones were isolated, and two highly polymorphic simple sequence repeat regions (GLP-1R-CA1 and GLP-1R-CA3) were identified. Polymerase chain reaction assays were developed to define alleles. For GLP-1R-CA1, 14 alleles were observed in African-Americans (heterozygosity [het] = 0.78) and 6 alleles in Caucasians (het = 0.67). For GLP-1R-CA3, 16 alleles were observed in African Americans (het = 0.89) and 8 alleles in Caucasians (het = 0.83). By genotyping all members of the 40 reference Centre d'Etude du Polymorphisme Humain pedigrees at GLP-1R-CA3, the human GLP-1 receptor gene was uniquely placed on chromosome 6p between GLO1 and D6S19, 20.4 cM from human leukocyte antigen. To assess the possible role of the GLP-1 receptor gene in determining the genetic susceptibility to NIDDM, allelic frequencies of GLP-1R-CA1 and GLP-1R-CA3 were compared between African-American NIDDM patients (n = 95) and control subjects (n = 93). The frequencies did not differ between the two groups at either GLP-1R-CA1 or GLP-1R-CA3. The GLP-1 receptor gene simple-sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees (n = 16) with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jun
PMID:Human glucagon-like peptide-1 receptor gene in NIDDM. Identification and use of simple sequence repeat polymorphisms in genetic analysis. 819 59

Moderate impairment of learning and memory has been recognized as a complication of diabetes. The present study examined behavioral and electrophysiological measures of cerebral function in streptozotocin (STZ)-induced diabetic rats. Behavioral testing consisted of a spatial learning task in a water maze. Electrophysiological testing consisted of in vitro assessment of hippocampal long-term potentiation (LTP), an activity-dependent form of synaptic plasticity, which is believed to be related to the cellular mechanisms of learning and memory. Two experiments were performed: the first with severely hyperglycemic rats and the second with moderately hyperglycemic rats. Rats were tested in the water maze 11 weeks after induction of diabetes. Next, LTP was measured in vitro in trained animals. Both spatial learning and LTP expression in the CA1 field of the hippocampus were impaired in severely hyperglycemic rats as compared with nondiabetic controls. In contrast, spatial learning and hippocampal LTP were unaffected in moderately hyperglycemic rats. The association of alterations in hippocampal LTP with specific learning impairments has previously been reported in conditions other than diabetes. Our findings suggest that changes in LTP-like forms of synaptic plasticity in the hippocampus, and possibly in other cerebral structures, are involved in learning deficits in STZ-induced diabetes. The beneficial effect of moderate glycemic control on both place learning and hippocampal LTP supports the significance of the relation between these two parameters and indicates that the development of the observed deficits may be related to the level of glycemic control.
Diabetes 1996 Sep
PMID:Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats. 877 32

We tested the hypothesis that the neuropathologic outcome following recovery from incomplete ischemia is similar in normoglycemia and diabetes. Incomplete global ischemia was induced for 20 min in two groups of dogs: (a) normoglycemic, nondiabetic controls (n = 11) and (b) chronic (3 months), diabetic hyperglycemic subjects (n = 12). Animals were allowed to recover from surgery for 7 days after which they were perfusion-fixed for neuropathology. On paraffin processed tissue stained with hematoxylin and eosin (H&E), ischemic neurons were counted and the per cent of cell damage determined. All control animals survived for 7 days postischemia. Four of 12 diabetic animals survived for 7 days, with the remaining eight diabetic dogs dying within the first 3 days. On day 7, the percentage of neurons showing ischemic cell change in the four diabetic survivors and the 11 nondiabetic controls was similar in the cerebellum, CA1, superior temporal gyrus, and caudate. However, diabetic dogs that did not survive the 7-day recovery period showed cerebellar swelling, reduced Purkinje cell densities, and herniation. During the 3 months prior to ischemia, morning (10.7 +/- 4.4 versus 11.2 +/- 5.2 mM) and afternoon (8.8 +/- 5.0 versus 9.4 +/- 5.3 mM) blood glucose levels in the four surviving and eight nonsurviving diabetic animals, respectively, were similar. However, preischemic blood glucose was significantly elevated in animals that did not survive (7.8 +/- 2.8 versus 15.8 +/- 7.3 mM in survivors and nonsurvivors, respectively). This study shows that diabetic animals surviving 7 days postischemia and nondiabetic controls have similar neuropathology. However, diabetic animals in which glucose control deteriorated during the 24-h prior to ischemia did not survive, possibly due to severe hindbrain edema. These results show that in diabetes, blood glucose control immediately prior to incomplete global brain ischemia is an important determinant of morbidity and neuropathology.
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PMID:Diabetic chronic hyperglycemia and neurologic outcome following global ischemia in dogs. 889 96

The mechanisms by which diabetes impairs cognitive function are not well-established. In the present study, we determined the electrophysiological and biochemical nature of disturbances in the mechanism of long-term potentiation (LTP) in diabetic rats. As previously reported, the administration of streptozotocin (STZ) was found to reduce the magnitude of LTP in the CA1 region of the hippocampus, while the same treatment did not interact with the capacity of the hippocampus to generate long-term depression induced by low-frequency stimulation. In addition, STZ treatment did not modify the component of excitatory postsynaptic potentials mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, suggesting that NMDA receptor function remained intact in STZ-treated slices. At the biochemical level, the capacity of calcium to increase [3H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (3H-AMPA) binding to glutamate/AMPA receptors in rat brain tissue sections was markedly affected in most regions of the hippocampus of STZ-treated rats. Moreover, changes in 3H-AMPA binding properties elicited by both exogenous phospholipase A2 and melittin, a potent activator of endogenous phospholipases, were also altered in synaptoneurosomes from diabetic rats. Taken together, the present data suggest that the loss of LTP maintenance in STZ-treated rats is more likely the result of disruption of calcium-dependent processes that are suspected to modulate postsynaptic AMPA receptors during synaptic potentiation. Understanding the biochemical factors participating in the impairment of AMPA receptor modulation might provide important clues revealing the very basis of memory deficits in diabetes.
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PMID:Impaired modulation of AMPA receptors by calcium-dependent processes in streptozotocin-induced diabetic rats. 936 22

Evoked field potentials were recorded in the CA3, CA1 and dentate gyrus (DG) regions of hippocampal slices from rats injected with streptozotocin (STZ; 60 mg/kg i.p.), to detect whether STZ-induced diabetes entails changes in hippocampal excitability. No change in hippocampal responsiveness was observed in slices from diabetic rats, up to 3 weeks post-STZ. Repetitive population spikes (PSs) reminiscent of an epileptiform hyperexcitability were, however, recorded in CA3 > CA1 > DG areas after more than 4 weeks ('long-term') post-STZ, although the maximal amplitudes were not different in STZ-diabetic versus control rats. Intracellular recordings on CA3 pyramidal neurons confirmed that fimbrial stimulation evokes significantly more action potentials in neurons from 'long-term' STZ-diabetic versus control rats. This is the first report of the appearance of repetitive hippocampal responses, particularly in the seizure-prone CA3 area, as a long-term consequence of hyperglycemic STZ treatment in rat.
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PMID:Hippocampal slices from long-term streptozotocin-injected rats are prone to epileptiform responses. 973 91

Hyperglycemia is known to aggravate ischemic brain damage. The present experiments were undertaken to explore whether hyperglycemia caused by streptozotocin-induced diabetes exacerbates brain damage following transient brain ischemia as it does in animals acutely infused with glucose. Experimental diabetes was induced by injection of streptozotocin in rats which were subjected to 10 min of forebrain ischemia either 1 week (1-wk) or 4 weeks (4-wk) after the induction of diabetes. Normoglycemic rats exposed to the same duration of ischemia and sham-operated diabetic rats served as controls. The animals underwent evaluation of clinical outcome and histopathological analysis of brain damage. Postischemic seizures developed in 35.3 and 42.1% of 1-wk and 4-wk diabetic hyperglycemic animals, respectively. The incidence of seizure was not different between the two groups. None of the diabetic animals with plasma glucose concentrations below 12 mM exhibited seizure activity. The extent and distribution of brain damage were similar between 1-and 4-wk diabetic animals. In the CA1 and in the subicular regions of hippocampus, both diabetic hyperglycemic and normoglycemic animals showed 70-80% cell death. Diabetic hyperglycemic animals had more severe neuronal necrosis in the parietal cortex than normoglycemic animals. In diabetic hyperglycemic animals, neuronal damage involved additional brain structures, e.g., cingulate cortex, thalamus nuclei, substantia nigra, pars reticulata, and the hippocampal CA3 sector, i.e., structures in which neurons were not affected in normoglycemic ischemic subjects at this duration of ischemia. These findings demonstrate that diabetic hyperglycemic animals frequently develop postischemic seizures and that streptozotocin-induced hyperglycemia results exacerbated postischemic brain damage of the same density and distribution as in acutely glucose-infused animals.
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PMID:Effects of streptozotocin-induced hyperglycemia on brain damage following transient ischemia. 974 9

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain.
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PMID:Perinatal brain iron deficiency increases the vulnerability of rat hippocampus to hypoxic ischemic insult. 991

Streptozotocin-diabetic rats, an animal model for diabetes mellitus, show learning deficits and impaired long-term potentiation in the CA1-field of the hippocampus. The present study aimed to further characterize the effects of streptozotocin-diabetes on N-methyl-D-aspartate receptor-dependent long-term potentiation in the CA1-field, to extend these findings to N-methyl-D-aspartate receptor-dependent and independent long-term potentiation in other regions of the hippocampus and to examine effects on long-term depression. First, the effect of diabetes duration on long-term potentiation in the CA1-field was determined. A progressive deficit was observed after a diabetes duration of six to eight weeks, which reached a maximum after 12 weeks of diabetes and remained stable thereafter. Next, long-term potentiation was examined in the dentate gyrus and in the CA3-field after 12 weeks of diabetes. Both were found to be impaired compared to controls. Finally, long-term depression was examined in the CA1-field of the hippocampus after 12 weeks of diabetes and found to be enhanced in slices from diabetic rats compared to controls. Changes in synaptic plasticity were observed in hippocampal slices from streptozotocin-diabetic rats. Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation was impaired in the CA1-field and dentate gyrus and expression of N-methyl-D-aspartate receptor-independent long-term potentiation was impaired in the CA3-field. In contrast, expression of long-term depression was facilitated in CA1. It is suggested that this combination of changes in plasticity may reflect alterations in intracellular signalling pathways.
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PMID:Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. 1021 75


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