Passage
Diabetic nephropathy (kidney disease) is characterized in part by a significant decrease in the glomerular filtration rate. Podocytes are differentiated cells that surround the glomerular capillaries and counteract the pressure of blood filtration. Hyperglycemia (elevated blood glucose) and capillary hypertension (high blood pressure) , both of which are common in diabetic patients, can subject podocytes to mechanical stress. This mechanical stress has been shown to regulate glucose uptake by podocytes, possibly by altering the production of glucose transport (GLUT) proteins.Researchers investigating GLUT2 and GLUT4 expression in rat podocytes measured the impact of mechanical stress on glucose uptake. Cells were grown for 4 hours on membranes exposed to atmospheric (atm) or high air pressure (HP) to mimic mechanical stress. Antibodies specific to GLUT2 and GLUT4 were used to visualize the expression of each under normal glucose (NG) and hyperglycemic (HG) conditions, and to assess the effect of mechanical stress on expression. The uptake of a radiolabeled glucose analogue, [³H]-2-deoxy-D-glucose (3H-2DG) , was then determined. The quantity of 3H-2DG transported by each GLUT protein was directly proportional to the cell surface expression.
Figure 1 Cell surface expression of GLUT transporters in response to mechanical stress and varying glucose concentration.In vivo studies have shown that transport via GLUT2 is noninducible and depends only on extracellular glucose concentrations. However, GLUT4-mediated uptake is induced by insulin binding and occurs under high glucose conditions when insulin is released. The standard K_m values for GLUT2 and GLUT4 are 19.4 and 4.3 mM, respectively, at normal blood glucose levels after a meal (~7.8 mM) . The data shown in Figure 2 represent the combined kinetic properties of both transporters.
Figure 2 Plot of glucose uptake in podocytes with and without mechanical stress.
Adapted from Lewko, B., Bryl, E., Witkowski, J. M., Latawiec, E., Angielski, S., & Stepinski, J. (2005) . Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes. Nephrology Dialysis Transplantation, 20(2) , 306-311.
-Which mechanism best describes how insulin could alleviate capillary hypertension in diabetic patients?

Question

Passage
Diabetic nephropathy (kidney disease) is characterized in part by a significant decrease in the glomerular filtration rate. Podocytes are differentiated cells that surround the glomerular capillaries and counteract the pressure of blood filtration. Hyperglycemia (elevated blood glucose) and capillary hypertension (high blood pressure) , both of which are common in diabetic patients, can subject podocytes to mechanical stress. This mechanical stress has been shown to regulate glucose uptake by podocytes, possibly by altering the production of glucose transport (GLUT) proteins.Researchers investigating GLUT2 and GLUT4 expression in rat podocytes measured the impact of mechanical stress on glucose uptake. Cells were grown for 4 hours on membranes exposed to atmospheric (atm) or high air pressure (HP) to mimic mechanical stress. Antibodies specific to GLUT2 and GLUT4 were used to visualize the expression of each under normal glucose (NG) and hyperglycemic (HG) conditions, and to assess the effect of mechanical stress on expression. The uptake of a radiolabeled glucose analogue, [³H]-2-deoxy-D-glucose (3H-2DG) , was then determined. The quantity of 3H-2DG transported by each GLUT protein was directly proportional to the cell surface expression.

Figure 1 Cell surface expression of GLUT transporters in response to mechanical stress and varying glucose concentration.In vivo studies have shown that transport via GLUT2 is noninducible and depends only on extracellular glucose concentrations. However, GLUT4-mediated uptake is induced by insulin binding and occurs under high glucose conditions when insulin is released. The standard K_m values for GLUT2 and GLUT4 are 19.4 and 4.3 mM, respectively, at normal blood glucose levels after a meal (~7.8 mM) . The data shown in Figure 2 represent the combined kinetic properties of both transporters.

Figure 2 Plot of glucose uptake in podocytes with and without mechanical stress.
Adapted from Lewko, B., Bryl, E., Witkowski, J. M., Latawiec, E., Angielski, S., & Stepinski, J. (2005) . Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes. Nephrology Dialysis Transplantation, 20(2) , 306-311.
-Which mechanism best describes how insulin could alleviate capillary hypertension in diabetic patients?

Quizplus · Accepted Answer

11ecba2d_0e7c_d7bf_a3bf_0386e656472f_MD0008_00 According to the passage, capillary hypertension (high blood pressure) increases the mechanical stress on podocytes. In diabetic patients, high blood glucose levels contribute to rising blood pressure in capillaries. Insulin administration reduces the concentration of glucose in the blood by increasing glucose uptake and consumption. Cells obtain glucose through transporters such as GLUT4 and GLUT2. However, the passage states that only GLUT4 is susceptible to regulation by insulin. GLUT4 is an inducible transporter that responds to the presence of insulin by increasing its uptake of glucose. Consequently, blood glucose concentrations are lowered and capillary hypertension decreases when insulin binding stimulates GLUT4. (Choice A) GLUT2 is not susceptible to insulin regulation. Therefore, the concentration of glucose inside cells with GLUT2 receptors will not be altered by insulin. (Choices C and D) Glucokinase is the enzyme that converts glucose into glucose-6-phosphate in the first step of glycolysis. The release of insulin stimulates glucokinase and results in an increase in glucose-6-phosphate production that consumes the glucose within the cell. As a result, glucose uptake increases and blood glucose levels decrease. Educational objective: Insulin reduces blood glucose concentrations by increasing the rate of glucose uptake and glucose consumption. Glucokinase converts glucose into glucose-6-phosphate in the first step of glycolysis. Insulin release stimulates glucokinase and increases the production of glucose-6-phosphate.

Passage Diabetic Nephropathy (Kidney Disease) Is Characterized in Part by a a Significant