Passage
Renal reabsorption of glucose is facilitated by sodium-glucose linked transporters (SGLTs) , which are secondary active transport proteins located in the apical membrane of the proximal tubular cells in the kidney. SGLT activity determines the transport maximum of glucose T_m, the maximum rate at which the kidneys can reabsorb glucose.Excretion of glucose in the urine (glycosuria) occurs when the glomerular filtration rate (GFR) of glucose exceeds the T_m. Glycosuria is a symptom of diabetes mellitus, a disease marked by hyperglycemia (elevated serum glucose) . Uncontrolled hyperglycemia can damage the nerves that innervate urinary tract musculature, resulting in urinary retention (inability to fully empty the bladder) or incontinence (involuntary urine leakage) .Canagliflozin is a SGLT inhibitor used for the treatment for diabetes. The effect of canagliflozin on renal glucose reabsorption was tested in a glucose infusion experiment in patients with type 2 diabetes mellitus (T2DM) . First, researchers measured the participants' fasting serum glucose levels (average ~80 mg/dL) and then began a continuous intravenous infusion of a glucose solution. The rate of glucose infusion was adjusted such that blood glucose concentration steadily rose to 300 mg/dL. Blood and urine glucose concentrations were measured at 30-minute intervals. The experiment was later repeated in the same patients following canagliflozin administration (100 mg, once a day for seven days) . The results of both trials are shown in Figure 1.
Figure 1 Mean urine glucose excretion versus blood glucose concentration in patients with T2DM, with and without canagliflozin treatmentResearchers then estimated the new T_m of glucose following canagliflozin treatment (Figure 2) . Canagliflozin was found to also lower fasting blood glucose in individuals with T2DM. Side effects included weight loss, increased urinary frequency, excessive thirst, and blood pressure reduction.
Figure 2 Mean rate of renal glucose reabsorption versus plasma glucose concentration in patients with T2DM, with and without canagliflozin treatment
-Urinary retention in patients with poorly controlled diabetes mellitus is most likely the result of nerve damage impairing smooth muscle contraction in which of the following structures?

Question

Passage
Renal reabsorption of glucose is facilitated by sodium-glucose linked transporters (SGLTs) , which are secondary active transport proteins located in the apical membrane of the proximal tubular cells in the kidney. SGLT activity determines the transport maximum of glucose T_m, the maximum rate at which the kidneys can reabsorb glucose.Excretion of glucose in the urine (glycosuria) occurs when the glomerular filtration rate (GFR) of glucose exceeds the T_m. Glycosuria is a symptom of diabetes mellitus, a disease marked by hyperglycemia (elevated serum glucose) . Uncontrolled hyperglycemia can damage the nerves that innervate urinary tract musculature, resulting in urinary retention (inability to fully empty the bladder) or incontinence (involuntary urine leakage) .Canagliflozin is a SGLT inhibitor used for the treatment for diabetes. The effect of canagliflozin on renal glucose reabsorption was tested in a glucose infusion experiment in patients with type 2 diabetes mellitus (T2DM) . First, researchers measured the participants' fasting serum glucose levels (average ~80 mg/dL) and then began a continuous intravenous infusion of a glucose solution. The rate of glucose infusion was adjusted such that blood glucose concentration steadily rose to 300 mg/dL. Blood and urine glucose concentrations were measured at 30-minute intervals. The experiment was later repeated in the same patients following canagliflozin administration (100 mg, once a day for seven days) . The results of both trials are shown in Figure 1.

Figure 1 Mean urine glucose excretion versus blood glucose concentration in patients with T2DM, with and without canagliflozin treatmentResearchers then estimated the new T_m of glucose following canagliflozin treatment (Figure 2) . Canagliflozin was found to also lower fasting blood glucose in individuals with T2DM. Side effects included weight loss, increased urinary frequency, excessive thirst, and blood pressure reduction.

Figure 2 Mean rate of renal glucose reabsorption versus plasma glucose concentration in patients with T2DM, with and without canagliflozin treatment
-Urinary retention in patients with poorly controlled diabetes mellitus is most likely the result of nerve damage impairing smooth muscle contraction in which of the following structures?

Quizplus · Accepted Answer

11ecba2d_0fa7_74e7_a3bf_41bf44278bdb_MD0008_00 After urine is concentrated in the nephron, it is funneled from the collecting ducts into the renal calyces. The calyces then merge at the renal pelvis, which marks the beginning of the ureter (the tube connecting the kidneys to the bladder). Urine is stored in the bladder until filled, after which it exits the body via the urethra in a process called urination. Urination is controlled by musculature lining the urinary tract. During urine collection, the detrusor muscle (the layer of smooth muscle lining the bladder) is relaxed. At the same time, the internal urethral sphincter (IUS, a ring of smooth muscle surrounding the urethra) and the external urethral sphincter (EUS, a ring of striated muscle downstream of the IUS) are contracted to prevent urine flow down the urethra. The detrusor and IUS are under involuntary control; the EUS is under voluntary control. During urination, activity within stretch receptors in the bladder leads to: Contraction of the detrusor muscle, which pushes urine out of the bladder and into the urethra. Relaxation of the IUS, which opens the urethra and allows urine to pass. Nerve damage that impairs the contraction of the detrusor muscle of the bladder would impair emptying of the bladder and lead to urinary retention. (Choice B) Urine is able to pass through the remainder of the urethra and out the body when the EUS is relaxed. When contracted, both the IUS and EUS block urine flow through the urethra. Inability to contract these muscles due to nerve damage would facilitate, not impair, urine flow. (Choice C) Diminished stimulation of the smooth muscles in the kidney due to nerve damage may alter the rate of urine production but would not affect the process of urination. (Choice D) Decreased contraction of smooth muscles in the ureter due to nerve damage may affect urine collection in the bladder. However, the ability to urinate, which is under control of the detrusor muscle, IUS, and EUS, would not be affected. Educational objective: Urine flows from the kidney to the bladder through the ureter. Once the bladder is full, urine exits the body via the urethra through the process of urination. Urination is controlled by the detrusor muscle (smooth muscle lining of the bladder), the internal urethral sphincter, and the external urethral sphincter.

Passage Renal Reabsorption of Glucose Is Facilitated by Sodium-Glucose Linked Transporters