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)

The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g b.wt.) was orally administered daily to alloxan-diabetic rats for 4 weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (P<0.05) increased in plasma of alloxan-diabetic rats compared with the control group. In contrast, total protein and albumin were significantly decreased by 25 and 46%, respectively, versus control. Treatment of the diabetic rats with repeated doses of any one of the three herb suspensions could restore the changes of the above parameters to their normal levels after 4 weeks of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AlP) activities were significantly (P<0.05) increased in the plasma of alloxan-diabetic rats. However, acetylcholinesterase activity was significantly (P<0.05) decreased in the plasma compared with the control group, whereas, such activity did not change in brain. The activities of AST, ALT and LDH were significantly (P<0.05) decreased in the liver of alloxan-diabetic rats by 58, 21 and 40%, respectively, and such activities increased in testes by 39, 26 and 26%, respectively, compared with the control group. Also, brain LDH was significantly (P<0.05) increased. Treatment of the diabetic rats with the aqueous suspension of the tested herbs restored the activities of the above enzymes to their normal level in plasma, liver and testes. The present results showed that the herb suspensions exerted antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.
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PMID:Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats. 1178 59

The recent development of acetylcholinesterase inhibitors to treat patients with Alzheimer's disease has increased interest in the use of biochemical markers for the early detection and diagnosis of dementia, but only the measurement of the protein 14-3-3 in cerebrospinal fluid (CSF) to help diagnose sporadic Creutzfeldt-Jakob disease has become accepted clinical practice. CSF concentrations of tau protein and beta-amyloid peptide 42 have been widely investigated as potential diagnostic tests for Alzheimer's disease, but neither has shown sufficient sensitivity and specificity for clinical use. Preliminary investigations suggest that beta-amyloid peptide 42 may be useful in monitoring disease progression, but this needs to be verified. In addition, biochemical investigations may help to identify the small number of patients with treatable causes of dementia such as hypothyroidism and vitamin B12 deficiency, as well as any other compounding condition such as anaemia or diabetes mellitus that increase morbidity.
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PMID:Biochemical investigations in patients with dementia. 1203 95

Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors can produce antinociception. However, the mechanisms of the action of cholinergic agents in the spinal cord are not fully understood. Activation of spinal muscarinic receptors evokes gamma-aminobutyric acid (GABA) release, which reduces the glutamatergic synaptic input to dorsal horn neurons through GABA(B) receptors. In this study, we determined the functional role of spinal GABA(B) receptors in the antinociceptive action of intrathecal cholinergic agents in normal rats and in a rat model of diabetic neuropathic pain. Diabetes was induced by intraperitoneal streptozotocin in rats. The intrathecal catheter was inserted with its tip positioned at the lumbar spinal level. Nociceptive threshold was measured by the paw withdrawal latency in response to a radiant heat stimulus in normal rats. Mechanical allodynia in diabetic rats was determined by von Frey filaments applied to the hindpaw. The effect of intrathecal muscarine or neostigmine was examined through pretreatment with the specific GABA(B) receptor antagonist, CGP55845, or its vehicle. Intrathecal injection of muscarine or neostigmine significantly increased the withdrawal latency in response to a heat stimulus in normal rats and the withdrawal threshold in response to application of von Frey filaments in diabetic rats. Intrathecal pretreatment with CGP55845 significantly attenuated the effect of both muscarine or neostigmine in normal rats. Furthermore, the antiallodynic effect of intrathecal neostigmine and muscarine was largely eliminated by CGP55845 in diabetic rats. These data suggest that the GABA(B) receptors in the spinal cord mediate both the antinociceptive and antiallodynic actions of intrathecal muscarine or neostigmine in normal rats and in a rat model of diabetic neuropathic pain. This study provides new functional evidence that activation of spinal GABA(B) receptors is one of the important mechanisms underlying the antinociceptive action of intrathecal cholinergic agents.
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PMID:Spinal GABAB receptors mediate antinociceptive actions of cholinergic agents in normal and diabetic rats. 1259 Nov 21

Between 20 and 35% of all dementias are vascular in origin, their etiology is due to cerebrovascular disease and the risk factors are known (e.g. hypertension, diabetes, smoking, or hyperlipidemia). Primary and secondary preventions are the basis of therapeutics. Symptomatic treatment is emerging, notably in the field of cognitive disorders. In that respect, monoamine oxidase inhibitors, and more recently acetylcholinesterase inhibitors, are in the process of being recognized as first-line treatments of established vascular dementia.
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PMID:Drugs and vascular dementia. 1271 93

Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors produce effective pain relief. Intrathecal injection of a small dose of neostigmine produces a profound antiallodynic effect in rats with diabetic neuropathy. However, the mechanisms of increased antinociceptive effect of cholinergic agents on diabetic neuropathic pain are not clear. In the present study, we tested the hypothesis that spinal muscarinic receptors are up-regulated in diabetes. The withdrawal threshold of the hindpaw in response to noxious heat and pressure stimuli was determined in streptozotocin-induced diabetic and age-matched normal rats. Muscarine-stimulated guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding was used to assess the change of functional muscarinic receptors in the spinal cord in diabetes. The [3H]AF-DX 384 membrane binding was performed to determine the number and affinity of spinal cord M2 muscarinic receptors in normal and diabetic rats. We found that the antinociceptive effect of intrathecal 2 to 12 mug muscarine in diabetic animals was potentiated significantly compared with that in normal animals. The maximal muscarine-stimulated [35S]GTPgammaS binding was 112.5 +/- 8.3% in normal rats and 168.8 +/- 12.1% (P < 0.05) in diabetic rats. Although the KD value (2.9 nM) was similar in both groups, the Bmax of [3H]AF-DX 384 membrane binding was significantly higher in diabetic than in normal rats (255.2 +/- 5.9 versus 165.9 +/- 3.5 fmol/mg protein, P < 0.05). Collectively, these data strongly suggest that the muscarinic receptor is up-regulated in the dorsal spinal cord in diabetic rats. This finding probably accounts for the increased efficacy of the antinociceptive effect of intrathecal muscarinic agonists in diabetic neuropathic pain.
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PMID:Up-regulation of spinal muscarinic receptors and increased antinociceptive effect of intrathecal muscarine in diabetic rats. 1296 47

Ischemic or hemorrhagic cerebrovascular disease (CVD) produces injury of brain regions important for executive function, behavior, and memory leading to decline in cognitive functions and vascular dementia (VaD). Cardiovascular disease may cause VaD from hypoperfusion of susceptible brain areas. CVD may worsen degenerative dementias such as Alzheimer disease (AD). Currently, the global diagnostic category for cognitive impairment of vascular origin is vascular cognitive disorder (VCD). VCD ranges from vascular cognitive impairment (VCI) to VaD. The term VCI is limited to cases of cognitive impairment of vascular etiology, without dementia; VCI is equivalent to vascular mild cognitive impairment (MCI). Risk factors for VaD include age, hypertension, diabetes, smoking, cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, sleep apnea, infection, and high C-reactive protein. Research on biomarkers revealed increased CSF-NFL levels in VaD, whereas CSF-tau was normal. CSF-TNF-alpha, VEGF, and TGF-beta were increased in both AD and VaD. VaD shows low CSF acetylcholinesterase levels. This condition responds to acetylcholinesterase inhibitors, confirming the central role of cholinergic deficit in its pathogenesis. Evidence strongly suggests that control of vascular risk factors, in particular hypertension, could prevent VaD.
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PMID:Vascular dementia. Advances in nosology, diagnosis, treatment and prevention. 1587 77

Whether high-cholesterol diets (HCD) induce a high incidence of memory deficits in diabetes requires to be established; if so, whether they induce impairments of memory acquired in the pre-diabetic stage as well as in the diabetic stage also needs to be elucidated, and part of the related mechanisms involved in this dysfunction should be determined. The mice were grouped into: normal mice fed normal diets (NN), diabetic mice fed normal diets (DN), normal mice fed HCD (NH), and diabetic mice fed HCD (DH). Animals were subjected to Morris water maze testing: 1) Learning in the pre-diabetic stage and memory retrieval in the diabetic stage; 2) Learning and memory retrieval in the diabetic stage. Following water maze testing, biochemical parameters were estimated in the animals. The results showed that significant impairments of memory retrieval, acquired in the diabetic stage, were observed only in DH group, neither in DN nor NH group in a short term compared with NN group. Biochemical parameters including fasting blood glucose, lipid peroxidation productions and acetylcholinesterase activities in frontal cortex and hippocampus increased more rapidly in DH group than those in the rest. These results indicate that HCD impair the diabetic retention of memory, but neither the diabetic acquisition of memory nor the pre-diabetic retention of memory in diabetic mice in a short term. Controlled HCD may be a strategy to prevent the loss of memory in diabetic individuals after they have acquired new information.
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PMID:High-cholesterol diets impair short-term retention of memory in alloxan-induced diabetic mice, but not acquisition of memory nor retention of memory in prediabetic mice. 1590 67

We reported that a leaf extract (GLEt) obtained from an anti-diabetic plant, Gymnema montanum, an endangered species endemic to India, has anti-peroxidative and antioxidant effects on diabetic brain tissue in rats. Here we examined the effect of the extract on the activity of reduced brain and retinal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetic rats received GLEt orally (200 mg/kg bwt/d) for 12 wk, and changes in blood glucose, plasma insulin, the lipid peroxidation marker thiobarbituric acid-reactive substance (TBARS), and AChE and BChE activity were measured. The results confirmed prior reports that hyperglycemia significantly enhances TBARS levels in brain and retinal tissue and decreases AChE and BChE activity. Treatment with GLEt significantly reversed the impairment in enzymatic activity in addition to reducing the level of TBARS, suggesting that GLEt protects against the adverse effect of lipid peroxidation on brain and retinal cholinesterases. We suggest that GLEt could be useful for preventing the cholinergic neural and retinal complications of hyperglycemia in diabetes.
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PMID:Modulation of impaired cholinesterase activity in experimental diabetes: effect of Gymnema montanum leaf extract. 1618 84

1. The aim of the present study was to clarify the role of ginsenoside Rh2 as the active compound in Panax ginseng root for lowering plasma glucose in animals. 2. Plasma glucose was assessed using the glucose oxidase method. Changes in the levels of insulin and C-peptide in plasma were measured by ELISA using commercially available kits. 3. After intravenous injection into fasting Wistar rats for 60 min, ginsenoside Rh2 (0.1-1.0 mg/kg) decreased plasma glucose in a dose-dependent manner. In parallel with the decrease in plasma glucose, increases in plasma insulin levels, as well as plasma C-peptide, were observed in rats receiving the same treatment. These effects of Rh2 were reversed by atropine (0.1-1.0 mg/kg), but not affected by the ganglionic nicotinic antagonists pentolinium or hexamethonium (both at 7.5 mg/kg). 4. Disruption of synaptically available acetylcholine (ACh) using an inhibitor of choline uptake (hemicholinium-3; 1-10 microg/kg) or an inhibitor of vesicular ACh transport (vesamicol; 1.5-3.5 mg/kg) abolished the actions of Rh2. In addition, physostigmine (0.1-0.5 mg/kg), at a concentration sufficient to inhibit acetylcholinesterase, enhanced the actions of the ginsenoside Rh2. Thus, mediation of the effects of Rh2 to enhance insulin secretion by ACh released from nerve terminals can be considered. 5. Blockade of the increase in plasma insulin and the plasma glucose-lowering action of Rh2 by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP; 5-10 microg/kg) indicates the participation of muscarinic M(3) receptors. Increases in plasma C-peptide level induced by Rh2 were also sensitive to 4-DAMP. 6. The results of the present study suggest that ginsenoside Rh2 has the ability to increase insulin secretion as a result of the release of ACh from nerve terminals that then stimulates muscarinic M(3) receptors in pancreatic cells. This finding shows the mechanism for the plasma glucose-lowering action of ginsenoside Rh2, that is one of the major principles contained in P. ginseng root. Thus, ginsenoside Rh2 may be applied as an adjuvant for the management of diabetes.
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PMID:Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats. 1644 95

The cascade of Alzheimer's disease (AD) neurodegeneration is associated with persistent oxidative stress, mitochondrial dysfunction, impaired energy metabolism, and activation of pro-death signaling pathways. More recently, studies with human postmortem brain tissue linked many of the characteristic molecular and pathological features of AD to reduced expression of the insulin and insulin-like growth factor (IGF) genes and their corresponding receptors. We now demonstrate using an in vivo model of intracerebral Streptozotocin (ic-STZ), that chemical depletion of insulin and IGF signaling mechanisms combined with oxidative injury is sufficient to cause AD-type neurodegeneration. The ic-STZ-injected rats did not have elevated blood glucose levels, and pancreatic architecture and insulin immunoreactivity were similar to control, yet their brains were reduced in size and exhibited neurodegeneration associated with cell loss, gliosis, and increased immunoreactivity for p53, active glycogen synthase kinase 3beta, phospho-tau, ubiquitin, and amyloid-beta. Real time quantitative RT-PCR studies demonstrated that the ic-STZ-treated brains had significantly reduced expression of genes corresponding to neurons, oligodendroglia, and choline acetyltransferase, and increased expression of genes encoding glial fibrillary acidic protein, microglia-specific proteins, acetylcholinesterase, tau, and amyloid precursor protein. These abnormalities were associated reduced expression of genes encoding insulin, IGF-II, insulin receptor, IGF-I receptor, and insulin receptor substrate-1, and reduced ligand binding to the insulin and IGF-II receptors. These results demonstrate that many of the characteristic features of AD-type neurodegeneration can be produced experimentally by selectively impairing insulin/IGF functions together with increasing oxidative stress, and support our hypothesis that AD represents a neuro-endocrine disorder associated with brain-specific perturbations in insulin and IGF signaling mechanisms, i.e. Type 3 diabetes.
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PMID:Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. 1662 31


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