Regulatory Roles of FoxO Transcription Factors in Metabolism

Forkhead Box O （FoxO） transcription factors play an important role in modulating metabolic functions. FoxOs,which are conserved among species and are regulated by the insulin signaling pathway,are usually expressed in insulin-sensitive tissues,including the liver,pancreas,skeletal muscle and gastrointestinal （GI） tract. During calorie restriction or starvation, FoxOs are predominantly localized to the cell nucleus where they activate transcription to increase hepatic gluconeogenesis,decrease insulin secretion,increase food intake and stimulate skeletal muscle degradation to supply substrates for gluconeogenesis. In insulin re-sistance or excess calorie supply,FoxOs are inactivated and lose their transcriptional activity. FoxOs also regulate the development of insulin-sensitive tissues by controlling cell differentiation,proliferation and survival. In this paper,we review the metabolic and cell cyclerelated genes controlled by FoxOs in insulin-sensitive tissues as well as their metabolic effects. Further studies into the roles of FoxOs,and the underlying mechanisms,in insulin-sensitive tissues will strengthen our understanding about tissue development and energy metabolism.

Immunosuppressive therapy in pancreas and islet transplant: Need for simultaneous assessment of insulin sensitivity and secretion

Diabetes mellitus is a metabolic disease possible to treat via pancreas/islet transplantation but most immunosuppressive drugs are diabetogenic. In this letter, we review current up to date methods to assess insulin action and secretion (using the surrogate indexes) suggesting their use in large studies in populations of pancreas/ islets transplanted patients.

A NEW INSULIN-SENSITIVITY INDEX FOR EPIDEMIOLOGICAL STUDY

Insulin sensitivity(IS) is an important parameter in the study of the relationship between the

Synthesis of （S）-2-Ethoxy-3-Phenylpropanoic Acid Derivatives and Their Insulin-Sensitizing Activity

A series of （S）-2-ethoxy-3-phenylpropanoic acid derivatives were synthesized and their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Compounds 1b, 1d, 1e and 1f exhibited more potent insulin-sensitizing activity than rosiglitazone.

Diclofenac derivatives with insulin-sensitizing activity

A series of diclofenac derivatives were synthesized.The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3- L1 cells.The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drug rosiglitazone.