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Old 02-02-2011
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Arrow PPAR-gamma

A new drug is being developed for the treatment of diabetes. This drug activates the peroxisome proliferator-activated receptor gamma (PPAR-gamma), a nuclear receptor and transcription factor. Activation of this receptor would most likely result in which of the following?

A. Down regulation of leptin activity
B. Increased insulin release
C. Decreased insulin resistance
D. Increased free fatty acid levels
E. Down regulation of adiponectin
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Old 02-02-2011
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Answer is C.

Thiozolidinedioned activate PPAR-gamma; this leads to metabolism of fatty acids and improvement in insulin resistance.
Clofibrate binds PPRA-alpha and affects different aspects of lipid metabolism.

Reference: Kaplan lecture notes, Biochemistry: 2009-10 edition. Pages 73 and 74.
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Old 02-02-2011
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C is true!
i think all the answers will lead to elevation of blood glucose except C.
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Old 02-02-2011
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Old 02-02-2011
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Thiazolidinediones (TZD5) exert their glucose-lowering effect by decreasing insulin resistance. TZDs bind to peroxisome proliferator activated receptor gamma (PPAR-gamma), which is a transcriptional regulator of the genes involved in glucose and lipid metabolism. One of the most crucial genes regulated by PPAR-gamma is adiponectin, which is a cytokine secreted by fat tissue (adipocytokine). Adiponectin levels are low in type 2 diabetes which TZDs alter. As the glucose lowering effect of TZDs requires alteration in gene transcription and protein synthesis, it takes days to weeks after initiation of therapy to observe a significant reduction in glucose levels. TZDs do not cause hypoglycemia. The main side effects of TZDs are fluid retention, weight gain, and the precipitation of congestive heart failure from fluid retention.
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