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insulin signaling.pdf - Reader NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENC

ID: 60202 • Letter: I

Question

insulin signaling.pdf - Reader NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE PartII Insulin Resistance "In this lab we are focusing on insulin resistance; the primary cause of type-2 diabetes. This means that even through insulin is present in the blood stream, the cells don't respond as robustly. Type-2 diabetes occurs as a result of continuous insulin signaling due to genetics, poor diet, obesity, and lack of exercise. This continuous over stimulation of insulin signaling alters how the insulin receptor and its down-stream signaling pathways will respond to insulin. So that is what the lab looks at...insulin resistance and cell signaling." There have been lots of possible changes to insulin signaling proposed as the key mechanisms responsible for insulin resistance, but the reality is that insulin resistance isn't understood. So here is a list of possible research topics to investigate and determine their relative role in insulin resistance. Excerpt 4 Some of the documented changes in insulin signaling as a result of diabetes are (numbers refer to Figure 4 in Excerpt 3) Decreased insulin receptor kinase activity upon binding of insulin to the receptor (2). Decreased binding of signaling effectors to the insulin receptor due to o Less phosphorylation sites on the insulin receptor (3) o Feedback inhibition on the signaling molecule, preventing its binding to the insulin receptor Decreased signaling effector binding leads to defective downstream activation of the kinase cascade and second messenger signaling pathways (7), (8) Decreased GLUT4 (glucose transporter) fusion to the cell membrane and less glucose transported into the cell (4), (5) Questions 1. What is the general purpose of feedback inhibition? What is the problem if feedback inhibition happens when it isn't supposed to? it isnt supposed to 2. How do the effects of insulin resistance compound to decrease cellular responses to insulin? 3. Hypothesize a mechanism by which the GLUT4 transporter's fusion to the cell membrane could be decreased. 4. Consider the possible projects that Mia could study. a. Which project would you pick? b. Why do you think this project is important? c. What kind of experiments would you do? 4:52 PM 10/25/2015 Search the web and Windows

Explanation / Answer

Qs. Hypothesise a mechanism by which the GLUT4 transporter's fusion to cell membrane could be decreased.

As. If insulin is absent (diabetes/ or insulin receptor knock out mouse)---------> vesicles will not fuse to plasma membrane--------> GLUT4 transporters present on vesicles will not be exposed to the cell surface-------> GLUT4 transporters will remain inside the cell ---------> no glucose intake.