Insulin receptors in the brain: structural and physiological characterization.
ABSTRACT The present study was conducted to characterize insulin receptors and to determine the effects of insulin in synaptosomes prepared from adult rat brains. Binding of 125I-insulin to synaptosome insulin receptors was highly specific and time dependent: equilibrium binding was obtained within 60 minutes, and a t1/2 of dissociation of 26 minutes. Cross-linking of 125I-insulin to its receptor followed by SDS-PAGE demonstrated that the apparent molecular weight of the alpha subunit of the receptor was 122,000 compared with 134,000 for the liver insulin receptor. In addition, insulin stimulated the dose-dependent phosphorylation of exogenous tyrosine containing substrate and a 95,000 MW plasma membrane associated protein, in a lectin-purified insulin receptor preparation. The membrane associated protein was determined to be the beta subunit of the insulin receptor. Incubation of synaptosomes with insulin caused a dose-dependent inhibition of specific sodium-sensitive [3H]norepinephrine uptake. Insulin inhibition of [3H]norepinephrine uptake was mediated by a decrease in active uptake sites without any effects in the Km, and was specific for insulin since related and unrelated peptides influenced the uptake in proportion to their structural similarity with insulin. These observations indicate that synaptosomes prepared from the adult rat brain possess specific insulin receptors and insulin has inhibitory effects on norepinephrine uptake in the preparation.
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ABSTRACT: To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). Tertiary care rehabilitation setting. Patients (N=41; 29 men, 12 women; mean age, 49.5+/-21 y) with a posttraumatic vegetative or minimally conscious state, 47+/-24 days after the index traumatic event. Supplementation with BCAAs. Disability Rating Scale (DRS) as log(10)DRS. Fifteen days after admission to the rehabilitation department, the log(10)DRS score improved significantly only in patients who had received BCAAs (log(10)DRS score, 1.365+/-0.08 to 1.294+/-0.05; P<.001), while the log(10)DRS score in the placebo recipients remained virtually unchanged (log(10)DRS score, 1.373+/-0.03 to 1.37+/-0.03; P not significant). The difference in improvement of log(10)DRS score between the 2 groups was highly significant (P<.000). Moreover, 68.2% (n=15) of treated patients achieved a log(10)DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.Archives of physical medicine and rehabilitation 10/2008; 89(9):1642-7. · 2.18 Impact Factor
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ABSTRACT: 1. While many questions remain unanswered, it is now well documented that, contrary to earlier views, insulin is an important neuromodulator, contributing to neurobiological processes, in particular energy homeostasis and cognition. A specific role on cognitive functions related to feeding is proposed, and it is suggested that brain insulin from different sources might be involved in the above vital functions in health and disease. 2. A molecule identical to pancreatic insulin, and specific insulin receptors, are found widely distributed in the central nervous system networks related to feeding, reproduction, or cognition. 3. The actions of insulin in the central nervous system may be under both multilevel and multifactorial controls. The amount of blood insulin reaching the brain, brain insulin stores and secretion, potential local biosynthesis and degradation of the peptide, and insulin receptors and signal transduction can be affected by metabolic factors induced by nutrients, hormones, neurotransmitters, and regulatory peptides, peripherally or in the central nervous system. 4. Glucose and serotonin regulate insulin directly in the hypothalamus and may be of importance for its biological effects. Central mechanisms regulating glucose-induced insulin secretion show some analogy with the mechanisms operating in the pancreas. 5. A cross-talk between insulin and leptin receptors has been observed in the brain, and a regulation of central insulin actions, potentially via serotonin modulation, by leptin, galanin, melanocortins, and neuropeptide Y (NPY) is suggested. 6. A more complete knowledge of the biological role of insulin in brain function and dysfunction, and of the regulatory mechanisms involved in these processes, constitutes a real advancement in the understanding of the pathophysiology of metabolic and mental diseases and could lead to important medical benefits.Cellular and Molecular Neurobiology 01/2003; 23(4):873-874. · 2.29 Impact Factor