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Drastic abnormalities have been demonstrated to occur in cerebral glucose and energy metabolism in sporadic Alzheimer's disease, pointing to a primary disturbance in neuronal insulin and insulin receptor signal transduction and contributing to the causation of dementia. The compound streptozotocin (STZ) is known to inhibit insulin receptor function. The(More)
  • S. Hoyer
  • 1998
The hypothesis is forwarded that sporadic late-onset Alzheimer disease is caused by non-insulin dependent diabetes mellitus which is confined to the brain. This hypothesis is based on the findings of Frölich and coworkers (this volume) who clearly demonstrate a perturbation of the neuronal insulin/insulin receptor signal transduction pathway which is(More)
The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for(More)
In sporadic Alzheimer's disease (AD), a number of metabolic alterations to the brain have been observed soon after the onset of the initial clinical symptoms. In particular, impairments of glucose utilization and related metabolic pathways are prominent and well-established findings in incipient AD, resembling metabolic abnormalities such as have been found(More)
Glucose is the principal source for energy production in the brain, and undisturbed glucose metabolism is pivotally significant for normal function of this organ. Peripheral glucose metabolism is impaired by streptozotocin (STZ), which induces diabetes mellitus. In this investigation, we have studied the local effects of intracerebroventricular (i.c.v.) STZ(More)
The intracerebroventricular (icv) application of streptozotocin (STZ) in low dosage was used in 3-month-old rats to explore brain insulin system dysfunction. Three months following STZ icv treatment, the expression of insulin-1 and -2 mRNA was significantly reduced to 11% in hippocampus and to 28% in frontoparietal cerebral cortex, respectively. Insulin(More)
A growing body of evidence implicates impairments in brain insulin signaling in early sporadic Alzheimer disease (sAD) pathology. However, the most widely accepted hypothesis for AD aetiology stipulates that pathological aggregations of the amyloid beta (Abeta) peptide are the cause of all forms of Alzheimer's disease.(More)
Interactions of glucose and cognitive function have been reported both in the presence of elevated arterial blood glucose levels and with decreased cerebral glucose metabolism. In order to test the peripheral vs. central effects of this phenomenon, we induced irreversible hyperglycemia and depression of cerebral glucose metabolism in separate designs by(More)
The purpose of the present study was to investigate whether or not cerebral glucose utilization is changed locally after damage of the neuronal insulin receptor by means of intracerebroventricular (icv) streptozotocin (STZ) administered in a subdiabetogenic dosage (1.5 mg/kg bw.). STZ was administered at the start of the study, and 2 and 21 days later(More)
The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. These findings have not been confirmed in an experimental model related to sporadic Alzheimer's disease, for example rats(More)