Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a drug that has attained interest because of its ability to alleviate symptoms in Alzheimer's type of dementia, was found to stimulate insulin secretion from isolated rat pancreatic islets. The insulinotropic effect of the drug was observed at 8.3 mM but not at 3.3 mM glucose and was dependent on extracellular Ca++. From perifused 86Rb(+)-prelabeled islets, tacrine inhibited the fractional efflux of 86Rb+ at 3.3 mM glucose, but stimulated 86Rb+ efflux at 8.3 mM glucose. These effects persisted in the absence of extracellular Ca++. Tacrine also stimulated 45Ca++ efflux from perifused 45Ca(++)-prelabeled islets at 8.3 mM but had no effect on 45Ca++ efflux at 3.3 mM glucose or in the absence of extracellular Ca++. It is concluded that tacrine potentiates glucose-stimulated insulin secretion by a mechanism that is dependent on extracellular Ca++ and involves an increased Ca++ influx. The increased Ca++ influx is either secondary to a decreased K+ permeability induced by an inhibition of ATP-dependent K+ channels and/or due to a direct effect of tacrine on glucose-activated Ca++ channels.
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PMID:Effects of tacrine on insulin secretion and 86Rb+ and 45Ca++ efflux from rat pancreatic islets. 133

The neuropeptide galanin potently inhibits insulin release, hippocampal acetylcholine release and firing of locus coeruleus cells, and stimulates feeding and release of growth hormone. Galanin regulates K+ channels, adenylyl cyclase and phospholipase C by acting at Gi/Go protein-coupled high-affinity receptors. Galanin receptor agonists such as the N-terminal fragment galanin1-16 act synergistically with morphine in the somatosensory system and have potential analgetic application. Galanin antagonists may be useful therapeutic agents in endocrinology, neurology and psychiatry. The enhancing effect of such agents on hippocampal cholinergic function would be useful in treatment of Alzheimer's disease. Recent synthesis of a series of high-affinity galanin antagonists, reviewed, along with galanin's actions, by Tamas Bartfai and colleagues, opens the possibility of examining the functions of endogenous galanin and test the pharmacological usefulness of antagonism of galanin function in the endocrine, somatosensory and central nervous systems.
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PMID:Galanin and galanin antagonists: molecular and biochemical perspectives. 138 14

Elderly people in the United States represent an emerging high risk group for nutritional deficiencies. A magnesium deficit in the elderly can occur due to inadequate nutrient intakes, multiple drug use, or altered gastrointestinal function. Magnesium has been targeted as a risk factor for elderly people and has been implicated in the aging process. Data presented in this review confirm decreased availability of magnesium in the food supply, lower intakes of magnesium by elderly people, and widespread supplementation practices. Conflicting data exist regarding levels of magnesium in the blood and magnesium status in the elderly. It is not known to what extent suboptimal intakes may affect the aging process; however, magnesium-deficient conditions have been associated with neuromuscular and cardiovascular disorders, endocrine disturbances, insulin resistance and Alzheimer's disease.
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PMID:A review of magnesium intake in the elderly. A cause for concern? 159 Nov 45

The binding characteristics of radiolabelled beta-nerve growth factor ([125I]NGF) have been determined on membrane preparations of basal forebrain from Alzheimer's disease (AD) brain and age-matched normal brains. [125I]NGF binds in a specific fashion indicative of a single receptor and is not displaced with microM concentrations of cytochrome c, insulin or epidermal growth factor (EGF). The mean dissociation constant (Kd) and the mean capacity (Bmax) of the NGF receptor were not significantly different between the 5 AD and 5 normal basal forebrain samples examined. Choline acetyltransferase (ChAT) activity was significantly reduced (P less than or equal to 0.001) in AD cerebral cortical samples compared with normal tissue.
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PMID:Low affinity nerve growth factor receptor binding in normal and Alzheimer's disease basal forebrain. 170 88

An investigation was carried out to determine whether a disturbance of glycometabolism is associated with dementia of Alzheimer type (AD). The first part of the study was carried out on 108 AD patients and 57 normal controls (NCs). Neither the plasma level of insulin nor that of glucose differed significantly between the two groups before the oral glucose tolerance test (OGTT), whereas there was a significantly greater increase of the plasma insulin in the AD group than in the NC group after the OGTT. The second part of the study was carried out on 54 AD patients, 44 patients with vascular dementia (VD), and 26 NCs. Early in the morning after overnight fasting, there was no significant difference in the fasting plasma level of either glucose or insulin, or the cerebrospinal fluid (CSF) level of glucose, among the three groups, However, the CSF level of insulin was significantly higher in the AD group than in the other two groups. These results suggest that an abnormally high level of insulin, not only in the peripheral blood after OGTT load but also in the CSF after fasting, may be associated with the pathology of AD.
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PMID:Increased insulin levels after OGTT load in peripheral blood and cerebrospinal fluid of patients with dementia of Alzheimer type. 179 Feb 63

Global cerebral blood flow and the cerebral metabolic rates of oxygen, CO2, glucose and lactate were studied in 11 patients aged 61-78 years who had been clinically diagnosed as suffering from incipient late-onset dementia of the Alzheimer type (DAT), and in 7 patients aged 66-83 years, in whom advanced late-onset DAT had been diagnosed, using the Kety-Schmidt technique. In incipient late-onset DAT, the predominant abnormality was a 45% reduction in cerebral glucose utilization, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were diminished by only 17% and 18%, respectively. A severe imbalance between oxygen utilization and glucose utilization thus became obvious. In contrast, in advanced stages of late-onset DAT, this imbalance between oxygen and glucose utilization rates in the brain became smaller and smaller, and cerebral blood flow diminished markedly; these biological brain parameters finally all settled down at between 55% and 65% of the corresponding control values. The predominant abnormality in brain glucose utilization in incipient late-onset DAT may be associated with an impairment of its control mechanism(s), which are assumed to be either an influence of brain insulin action, or brain insulin receptor function, or both.
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PMID:Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incipient early-onset cases. 190 36

The somatostatinergic system has proven to be one of the best models of neuropeptide biology. Originally characterized as a hypothalamic regulator of growth hormone secretion, somatostatin also regulates the secretion of several other pituitary, pancreatic, and gastrointestinal (GI) hormones including thyrotropin-stimulating hormone, insulin, glucagon, and gastrin. Disorders in somatostatin metabolism have been proposed to contribute to the pathogenesis of Alzheimer's disease, epilepsy, GI motility disorders, and diabetes. On a more basic level, studies of somatostatin action have integrated divergent concepts of intracellular signal transduction. Advances in the understanding of somatostatin biosynthesis have had an impact on areas outside the field of endocrinology by providing new concepts of eukaryotic gene regulation. This report focuses on the transcriptional regulation of somatostatin gene expression. Two aspects of somatostatin gene transcription will be considered--regulated expression by second messengers and tissue-specific basal expression.
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PMID:Somatostatin gene regulation: an overview. 197 13

Recent data suggest a disturbance of some brain somatostatin neurons in Alzheimer's disease. Moreover, some endocrine activities known to be regulated by somatostatin, such as growth hormone, thyroid-stimulating-hormone, somatomedins, as well as insulin and glucose metabolism, also seem to be affected in some patients. It is speculated that these changes are due to a global CNS and endocrine somatostatin defect in Alzheimer's disease and that the described endocrine imbalance may indirectly be responsible for at least part of the CNS pathology.
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PMID:Somatostatin and Alzheimer's disease: a hypothesis. 287 94

A massive cerebral release of amino acids and ammonia was found in early-onset dementia of Alzheimer type. Aspartate and glycine were liberated in high concentrations, whereas glutamate remained rather unchanged. This excess cerebral protein catabolism is due to a 44% reduction in cerebral glucose metabolism. Whereas glutamate and other glucoplastic amino acids may substitute glucose, elevated aspartate may contribute to neuronal damage. The results are discussed with respect to a possible neuronal insulin/insulin receptor deficiency.
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PMID:Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. 292 84

Patients with Alzheimer's disease (AD) and matched controls fasted for 24 hours, and serial glucose, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon levels were measured. Patients with AD showed a glucose insulin correlation pattern over the 24 hours that differed from the control group. These differences may be secondary to weight loss or to other metabolic or nutritional factors affecting the AD patients.
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PMID:Metabolic changes in Alzheimer's disease. 328 Jun 43


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