“Mia, now that you understand the basics of signaling and the mechanisms it uses
ID: 541459 • Letter: #
Question
“Mia, now that you understand the basics of signaling and the mechanisms it uses, I want to talk about why this lab studies cellular signaling. You said that you had a family member with type-2 diabetes, right?”
“Yeah, my grandpa.”
“So how does diabetes affect his life?”
“Well, he is really careful what he eats and he goes for walks most days. He also has to check his blood glucose level all the time and he gives himself injections before most meals. And for some reason my mom has to remind him everyday to check his feet, but I never understood why.”
“Your grandpa’s goal is to keep his glucose levels balanced; it can’t be too high or too low. He checks his blood glucose to see if he needs to do something to change it. For instance, after people eat their blood glucose generally goes up. This causes the pancreas to release a signal known as insulin into the blood stream. In diabetics, the cellular signaling is messed up so it doesn’t work as well. So your grandpa is probably injecting himself with insulin or an insulin analogue.”
“So what you’re saying is that my grandpa controls his diabetes by controlling cellular signaling.”
“Yes, the effects of diabetes are varied and can be devastating. By changing signaling, they can be managed. You can see a list of resulting symptoms in the next excerpt (Excerpt 2). The symptoms occur for two reasons: 1) there are high glucose concentrations in the blood and 2) very little of the glucose is getting into the cell. Since glucose is an energy source and it needs to get into the cell to be used, the cells need to use something else for energy. What other things can the cell use for energy?”
“Well, I guess proteins or fats.”
“That’s right. The cells start using proteins, which leads to a buildup of ketoacids. As acids, what would they do to the pH in the blood?”
“The pH of the blood would decrease. Isn’t that bad? Don’t we want our pH to be around 7?”
“Yes, this lower pH is bad and it can damage lots of tissues, causing the symptoms listed in the next excerpt (Excerpt 2). This brings me to why your grandpa has to check his feet. One problem with diabetics is that they lose feeling in their feet, so if they get a blister on their foot they may not feel it. Then it may get infected because diabetics have poor wound healing, and if the infection isn’t noticed it may lead to amputation of the foot or leg.”
“I guess I’ll help my mom bother my grandpa to check his feet.”
Book excerpt 2
Diabetes affects 25.8 million people in the US. The number of young people that are annually diagnosed with diabetes is on the rise, with 15,600 diagnosed with type-1 diabetes and 3,600 diagnosed with type-2 diabetes. In 2007, the estimated annual cost of diabetes was $174 billion dollars. Average medical expenditures of individuals with diabetes are 2.3 times higher than people without diabetes. The major complications with diabetes are heart disease, stroke, high blood pressure, blindness, kidney disease, nervous system damage, and amputation.
Type-2 diabetes results from target cells that don’t respond as well to insulin. If untreated, type-2 diabetes leads to excess glucose in the blood. If cells cannot use glucose metabolism for energy, they can start breaking down protein. Excess protein metabolism can lead to a buildup of byproducts known as ketoacids. These ketoacids in combination with excess blood glucose can lead to a host of physiological problems including:
• Blurred vision blindness
• Weak immune system
• Fatigue
• Impaired cognitive function
• Kidney problems (frequent urination, dehydration) dialysis
• Irregular heartbeat heat attack
• Loss of sensation in limbs (especially feet)
• Coma/death
• Poor wound healing- with foot lesions amputation
“So now I want you to connect these ideas to diabetes and insulin signaling specifically.”
“Ok, what do you want me to do?”
“This afternoon, I want you to label this figure from the next excerpt on insulin signaling (below) to identify the different parts of a signaling pathway. I want you to label the signal, the receptor, the signal transduction, and the effects. This figure is labeled with the names of some of the proteins like MEK or MAPK but it’s not as important as realizing, for instance, that they are part of a kinase cascade. The thing that I want you to focus on is the different signaling modes and how they are all connected to the insulin receptor.”
Book excerpt 3
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 amino 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).
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).
Explanation / Answer
Answer The portion of the signaling cascade above labeled A is the signal pathway
As it is given in the question 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 amino 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).
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)
Related Questions
Navigate
Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.