Biochemistry

BCHM / BIOL 404 Fall, 2019 Midterm (Diabetes) 20 points

This is a take-home exam with six questions. Please submit your answers in a Word file through Canvas by 11:59 pm on Wednesday, October 23. Please try to synthesize your answers from material presented in class. You are free to use your notes, class overheads as well as printed or electronic reference. If you do use references, please cite them by providing the authors, article title, year, journal name, volume, year of publication, and page numbers. Please refrain from asking classmates or any other people for assistance. However, you are

perfectly welcome to ask the instructor questions in person or via email. Please use a 12-point font, single spacing and one-inch margins and adhere to the page limits stated.

If you feel that designing your own question will do a better job of letting you show off your knowledge, feel free to do so to replace one question with the exception of question #1. If you feel like our discussion of diabetes lead to you make a connection that is novel and / or interesting, that might provide an approach for designing a question. Please appreciate that like bull riding, the more complex the question you ask is, the higher your score may be.

1. [6 points] We have taken the approach of understanding diabetes beginning with the most severe pathology and working backwards toward the root cause. That is not to say that we arrived at the root cause since such an origin is not known. However, as best you can, construct a sequence of events in the other direction. That is, describe the earliest events in type 2 diabetes mellitus and how those lead to successive events that lead to the most severe pathologies. Your description may have forks in the road instead of being linear. That is fine. Please be clear about where the forks are. Please draw from the material presented in class as much as you can and refrain as best you can from looking for a reference that provides such a progression. I am hoping that in synthesizing the progression you will make connections that were not previously appreciated. Using references to augment the material presented in class is encouraged as time allows. Please cite any references that you use, provide many details, and limit your answer to two typed pages.

2. [3 points] Design a clinical study to determine if an aldose reductase inhibitor will slow the progression of the nephropathy associated with diabetes mellitus (either type). Please limit your answer to one page.

3. [3 points] Advanced glycation end products (AGEs) can impact cellular function by modifying the structure of proteins. Of the proteins we have discussed, choose two whose function may be directly altered by an AGE and explain how that alteration may fit in the development or progression of type 1 or type 2 diabetes mellitus. Please limit your answer to one page.

4. [3 points] What evidence supports there being a genetic component to type 2 diabetes mellitus? Choose one gene with alleles linked to type 1 or 2 DM and describe the mechanistic role of the respective role in diabetes development or progression. Please limit your answer to one typed page.

5. [2 points] Would a glucagon antagonist be a viable treatment for type 2 diabetes? Explain. Please limit your answer 2/3 of a typed page.

6. [3 points] Sulfonylurea is a drug that can bind a human receptor called SUR1. The subsequent signal cascade inhibits ATP-sensitive potassium channels.

a) Please describe if this drug will be useful to treat patients with type 1 diabetes mellitus? b) Will it be useful to treat patients with type 2 DM? - If you do propose its use for either, please c) offer and support a regimen for administering sulfonylurea in the course of a “typical” 24 hour day.

d) One concern about taking sulfonylurea is that it may promote weight game. Describe a possible mechanism for this.

Please limit your answer to one typed page.