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insulin-signaling[1].pdf. Adobe Acrobat Pro File Edit View Window Help Customize + | 10096 | Tools Sign Comment Insulin Signaling Click on Tools, Sign, and Comment to access additional features. Insulin binds to the insulin receptor (1); Receptor is activated, causing a conformation change known as dimerization (the coming together of two insulin receptors). Receptor adds a phosphate to amio acids (tyrosines) on the tail of the other insulin receptor in the pair (2). Signal transduction proteins interact with phosphate group (3). Interaction of the phosphate groups with all of the different signaling proteins occurs simultaneously, but each pathway will be discussed individually. Signaling proteins and pathways will cause the short-term and long-term changes in response to the increased glucose in the blood stream. One major short-term change is the fusion of vesicles containing glucose transporter (GLUT4) to the cell membrane (4). Once these transporters are part of the cell surface, glucose is transported into the cell (5). 9 Long-term cellular changes are caused by changes in gene transcription that result in specific proteins being made or not made. These pathways utilize many different signaling patterns, such as the direct activation of a transcription factor (T.F) (6), the release of second messenger (7), and the activation of a kinase cascade (8). All of these signaling pathways can result in the activation of transcription factors and their movement to the nucleus to activate transcription (9) Figure 4. Insulin 0 Insulin Re 0 EXTRACELLULAR INTRACELLULAR Vesicle Second Messenger PIP2 IP3, DAG inase MAPKCascade o t 9 DNA T.F. (Elk) US "Diabetes and Insulin Signaling" by Kristy J. Wilson Page 6 9:11 AM 10/19/2015Explanation / Answer
There is a network of intracellular signaling molecules associated directly or indirectly with the plasma membrane receptors. These receptors are typically protein in nature so that they cannot internalize by with substrate (insulin is also a peptide hormone), unlike lipids through the plasma membrane. Few molecules will involve in phosphorylation of signaling moieties and few will involve in dephosphorylation, based on substrate availability that results in activation or suppression of the pathway. Some molecules will dimerize upon activation, that carries the signal from the cytoplasm to nucleus.They will directly bind to DNA or some DNA binding proteins and regulates the expression respective genes in response to stimulus and need. Its regulation becomes multifactorial and unique from other signaling pathways. All the molecules will coordinate each other for regulation of gene expression that would be quite different from other hormone-mediated signalings. It gives unique figure of regulation to activate specific transcription factors that can specifically bind to respective DNA sequence to further expression and mRNA/protein production.
It is known that different tissues in the body attributed for different functions. Insulin typically involves in glucose and fat metabolism. For example, it promotes the glycogen synthesis in liver and glucose breakdown in muscles (of different organs). It suggests that excessive blood glucose convert into glycogen and store in the liver. In skeletal muscles, it increases the glycolysis for indeed of energy demand. It opposes the leptin production from adipocytes since, both acts on the brain and controls the food intake and energy balance. Insulin resistance leads to the obesity due to abnormal functioning of adipocytes that results in fat deposits.
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