%0 Journal Article
%T Anaesthesia generates neuronal insulin resistance by inducing hypothermia
%A Christian Holscher
%A Lidy van Aalten
%A Calum Sutherland
%J BMC Neuroscience
%D 2008
%I BioMed Central
%R 10.1186/1471-2202-9-100
%X We find that urethane- and ketamine-induced anaesthesia results in rapid activation of the phosphatidylinositol (PI) 3-kinase-protein kinase B (PKB) signalling pathway in the brain, increases tau phosphorylation while at the same time reducing basal activity of the Ras-ERK pathway. Subsequent injection of insulin does not alter the activity of either the PI 3-kinase or ERK signalling pathways, indicating a degree of neuronal molecular insulin resistance. However, if body temperature is maintained during anaesthesia then there is no alteration in the basal activity of these signalling molecules. Subsequent response of both pathways to insulin injection is restored.The data is consistent with a hypothermia related alteration in neuronal signalling following anaesthesia, and emphasises the importance of maintaining the body temperature of rodents when monitoring insulin (or growth factor/neurotrophic agent) action in the brain of anesthetised rodents.Insulin is produced by pancreatic ¦Â-cells, in response to rising plasma glucose levels, and initiates multiple metabolic changes to restore glucose homeostasis. A specific membrane glycoprotein acts as a high affinity sensor for insulin (insulin receptor (IR)) in many tissues (primarily liver, fat, muscle). The IR is expressed in many regions of the brain, including the hypothalamus, cortex, and hippocampus. Neuron specific deletion of the IR makes the animal more sensitive to diet induced obesity [1], implicating neuronal IR in the satiety response. Consistent with this, administration of insulin to the arcuate nucleus in the hypothalamus has significant effects on feeding and body weight [2-4].Epidemiological evidence suggests that whole body insulin resistance, related to obesity, increases the risk of Alzheimer's disease, as well as vascular dementia [5-7]. In addition, there are molecular links between the development of Type 2 diabetes (an insulin resistant state) and Alzheimers's disease [8]. For example, GSK3¦Â acti
%U http://www.biomedcentral.com/1471-2202/9/100