A 40-year-old woman has experienced chest pain on exertion for the past 2 months. A month ago, she had pneumonia with Streptococcus pneumoniae cultured from her sputum. On physical examination, she has a body mass index of 35. A random blood glucose value is 132 mg/dL. The next day, fasting blood glucose is 120 mg/dL, followed by a value of 122 mg/ dL on the following day. She is given an oral glucose tolerance test, and her blood glucose is 240 mg/dL 2 hours after receiving the standard 75-g glucose dose. On the basis of these findings, she is prescribed an oral thiazolidinedione (TZD) drug. After 2 months of therapy, her fasting blood glucose is 90 mg/ dL. The beneficial effect of TZD in this patient is most likely related to which of the following processes?
A 40-year-old woman has experienced chest pain on exertion for the past 2 months. A month ago, she had pneumonia with Streptococcus pneumoniae cultured from her sputum. On physical examination, she has a body mass index of 35. A random blood glucose value is 132 mg/dL. The next day, fasting blood glucose is 120 mg/dL, followed by a value of 122 mg/ dL on the following day. She is given an oral glucose tolerance test, and her blood glucose is 240 mg/dL 2 hours after receiving the standard 75-g glucose dose. On the basis of these findings, she is prescribed an oral thiazolidinedione (TZD) drug. After 2 months of therapy, her fasting blood glucose is 90 mg/ dL. The beneficial effect of TZD in this patient is most likely related to which of the following processes?
π‘ Explanation
### **Core Concept**
The underlying pharmacological principle being tested is the mechanism of action of thiazolidinediones (TZDs), a class of oral hypoglycemic agents used to treat type 2 diabetes mellitus. Specifically, the question is asking about the process by which TZDs exert their beneficial effect on glycemic control.
### **Why the Correct Answer is Right**
Thiazolidinediones work by activating peroxisome proliferator-activated receptor-gamma (PPAR-Ξ³), a nuclear receptor that regulates the expression of genes involved in glucose and lipid metabolism. Activation of PPAR-Ξ³ leads to increased insulin sensitivity in peripheral tissues, particularly in skeletal muscle and adipose tissue. This results in improved glucose uptake by these tissues, reduced hepatic glucose production, and decreased glucose levels in the blood. In the context of this patient, the activation of PPAR-Ξ³ by the TZD drug has increased insulin sensitivity, allowing glucose to be taken up more efficiently by peripheral tissues, thereby lowering fasting blood glucose levels.
### **Why Each Wrong Option is Incorrect**
**Option A:** This option does not accurately describe the mechanism of action of TZDs. While it is true that TZDs can affect insulin secretion, this is not the primary mechanism by which they exert their beneficial effect on glycemic control.
**Option B:** This option is incorrect because TZDs do not primarily work by increasing the production of insulin.
**Option C:** This option is not accurate because while TZDs can affect glucose uptake in adipose tissue, this is not the primary mechanism by which they exert their beneficial effect on glycemic control.
### **Clinical Pearl / High-Yield Fact**
A key aspect of TZD therapy is that they can lead to fluid retention, which can increase the risk of heart failure in susceptible patients. Therefore, patients on TZD therapy should be monitored regularly for signs of fluid retention and heart failure.
### **Correct Answer:**
**C. Increased insulin sensitivity in peripheral tissues**
β Correct Answer: A. Activation of PPARg nuclear receptor in adipocytes
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