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. 2010 Dec 30;363(27):2667-9.
doi: 10.1056/NEJMcibr1012075.

Rosiglitazone, PPARγ, and type 2 diabetes

Barbara B Kahn  1 , Timothy E McGraw
Affiliations

Rosiglitazone, PPARγ, and type 2 diabetes

Barbara B Kahn et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Effects of Thiazolidinediones
Thiazolidinediones have an array of beneficial and harmful effects on multiple tissues. Some of the effects are direct, whereas others are indirect. Adipocyte differentiation is thought to be beneficial for several reasons, including the production of favorable adipokines by small adipocytes and the provision of an expanded storage depot for lipids so that they are not deposited ectopically. Different thiazolidinediones have variable effects on plasma lipid profiles.
Figure 2
Figure 2. A Comparison of PPARγ Activity in Lean and Obese Persons
Regulation of the activity of peroxisome-proliferator–activated receptor γ (PPARγ) in the healthy, lean state (Panel A) differs from regulation in the obese, insulin-resistant state (Panel B). Obesity, a high-fat diet, and distinct types of lipids and fatty acids induce the production of inflammatory cytokines, which activate cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates PPARγ on serine residue 273 and induces a transcriptional program that is distinct from that of unphosphorylated PPARγ. The differences include both induction and repression of gene sets (represented by A, B, and C), as compared with transcriptional programs in adipose tissue in the nonobese or insulin-sensitive state. In addition to activating PPARγ, certain antidiabetic PPARγ ligands also block CDK5 phosphorylation. This effect may potentially restore the PPARγ transcription program to that of the healthy lean state or preferentially activate insulin-sensitizing gene programs.
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