BMS 450 Lecture Notes - Diabetic Coma, Gestational Diabetes, Statin
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Based on “Morgan: A case of Diabetes” by Lisa Rubin and Clyde Freeman Herreid (National Center for Case Study Teaching in Science)
The Patient:
Morgan Water is a 27-year old Native American that lives on a reservation in Oklahoma. Nearly ¼ of Morgan’s tribe has diabetes but she has no direct family history of diabetes, heart disease, or other serious conditions. She is however obese (BMI = 32) and leads a sedentary lifestyle. Morgan has been suffering from an increasing persistence of symptoms including unusual thirst, dizziness, blurred vision, and numbness in her right foot. The symptoms have been developing over several months but as she is planning her wedding she attributed them to nerves. She is finally persuaded to see her family doctor. Her non-fasting blood glucose level was elevated so the doctor has her return the next morning for a fasting blood sample so they could more accurately measure her blood glucose and insulin. Her blood results are below:
Test | Morgan’s values | Normal range | Pre-Diabetic range | Diabetic range |
Plasma glucose, mg/dl | 260 | 70 -139 | 140 - 199 | ≥ 200 |
Fasting glucose, mg/dl | 140 | ≤ 99 | 100 - 125 | ≥ 126 |
A1C, % | 7.6 | ~ 5 | 5.7 – 6.4 | ≥ 6.5 |
Fasting Insulin, mIU/ml | 34 | 2 - 10 | 10 - 20 | ≥ 20 |
Question 1:
Based on her history and blood results, what do you think is the most likely diagnosis for Morgan?
A. Type I Diabetes Mellitus
B. Type II Diabetes Mellitus
C. Pre-Diabetes
D. Cardiovascular Disease
Question 2:
What is the cause of Morgan’s disease?
A. It is an auto-immune disorder that destroys the β-cells of her pancreas so she produces less
insulin than normal.
B. She has a genetic mutation that results in less insulin receptor being produced than normal.
C. She has developed insulin resistance, where her insulin receptors do not recognize the insulin her
body produces, likely due to her obesity.
D. There is no known cause, it can happen spontaneously.
Morgan is worried that she will have to spend the rest of her life giving herself injections but her doctor does not prescribe insulin injections.
Question 3:
Why would injections of insulin not help Morgan if she has hyperglycemia?
A. Her body is already producing excess insulin but not responding to it.
B. Her problem is with her insulin receptors responding to insulin.
C. Excess insulin will only exacerbate her insulin resistance.
D. All of the above.
Question 4:
Given Morgan’s metabolic state, which of the following pathways would you expect to be active in Morgan’s cells (select all that apply)?
A. Glycolysis
B. Gluconeogenesis
C. β-oxidation
D. Amino acid degradation
E. Protein synthesis
3. Equilibrium
Insulin resistance occurs when cells no longer bind insulin in a normal manner, thus inhibiting the cells from transporting glucose inside the cell. Without intercellular glucose the cells cannot produce energy to support life.
Let’s suppose part of your project requires you to study the equilibrium reaction between the new variation of insulin you synthesized and cell receptors on the walls of cells. This is the equilibrium expression you propose.
cell receptor + free insulin cell receptor-insulin complex
or in abbreviated terms
R + I R-I
You devise a method of measuring the free insulin in solution. You run two experiments under the same conditions, except one experiment uses your modified insulin and the other experiment uses normal insulin. Table 1 below provides the initial conditions of your experiment and Table 2 provides the data you collected after equilibrium was established.
Initial Conditions for both experiments – all environmental conditions are kept constant (e.g. temperature at 34oC, pressure at 1 atm, pH at 7.4). A single stock nutrient and cell receptor solution was prepared with a concentration of 70 uM. 50 mL the solution was used in all experiments. The insulins were added as powders, so the volumes essentially remained unchanged.
Table 1: Initial Experimental Conditions
Experiment 1 | Experiment Control |
[free modified insulin] = 100.0 uM | [free normal insulin] = 100.0 uM |
[cell receptor] = 70.0 uM | [cell receptor] = 70.0 uM |
Table 2: Unbound Free Modified Insulin and Unbound Free Normal Insulin Levels at Equilibrium
Experiment 1 | Experimental Control |
[free modified insulin] = 35.0 uM | [free normal insulin] = 50.0 uM |
Write the equilibrium expression for this reaction using [I] to represent the insulin concentration, [R] the cell receptor concentration, and [I-R] to represent the cell receptor-insulin complex concentration. (10 pts) Show all work.
Determine an equilibrium constant for both the modified insulin and the normal insulin reaction at 34oC based on the data above. (10 pts)
[free modified insulin] | [receptor] | [Insulin-receptor] | |
I | |||
C | |||
E |
[free normal insulin] | [receptor] | [Insulin-receptor] | |
I | |||
C | |||
E |
Which type of insulin binds more strongly to the cell receptor? Explain your answer. (10 pts)
Suppose the concentration of the receptor in the stock solution dropped to 50.0 uM. If you ran the experiment again with the same initial concentration of free modified insulin as above, what would you expect the free modified insulin’s equilibrium concentration to be? (10 pts)
[free modified insulin] | [receptor] | [Insulin-receptor] | |
I | |||
C | |||
E |
Can someone please help me with this? I dont understand what to fill in the ice tables.