IRIG: Incretin Safety in JAMA

Incretin are defined as a hormone produced in the gastrointestinal tract in response to food (especialy carbohydrates) intake, and stimulating insulin secretion in the presence of glucose. Presently, there are are two such hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Since incretin is able to reduce blood glucose and increase insulin sensitivity, GLP-1 has been a pharmalogical target in the control of glucose in clinics. Safety of GLP-1 analogues and GLP-1 enhancer (Dipeptidyl peptidase 4 inhibitors) has been a concern. In the current issue of JAMA, this issue is addressed in a review article. The conclusion is that "Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection". See detail in attached paper. 
 
By Jianping at PBRC

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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail:
yej@pbrc.edu
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IRIG: NYP jumps out of brain, article in Nature Medicine

Neuropeptide Y (NPY) is a neurotransmitter with well-known function in the stimulation of food intake in the brain. In ob/ob mice, expression of NPY is increased in the brain and this increase contributes to hyperphagia, which leads to obesity in ob/ob mice on a regular diet. It is generally believed that NPY is expressed in the brain, and acts locally in the brain. In the current issue of Nature Medicine, a new study suggests that NPY is able to act in the adipose tissue for development of central obesity in stress condition, such as cold or aggression. This peripheral activity of NPY includes stimulation of proliferation and differentiation of preadipocytes, promotion of angiogenesis and inhibition of lipolysis in adipose tissue. NYP is found to be released from sympathetic nerves in response to the stress. The study suggests a novel function of NPY. Attached is the paper and commentary.
 
This paper is also recommended by Drs. Eric Ravussin and Vishwa Dixit at PBRC.   
 
By Jianping at PBRC

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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail:
yej@pbrc.edu
|

IRIG: Macrophage as TZD target for insulin sensitization in Natureand JCI

TZD is a powerful medicine for improvement of insulin sensitivity in both human and animals. Adipocytes are generally believed as the primary target of TZD, which activates the nuclear receptor PPARg. PPARg expression is highest in adipocytes and adipocyte differentiation is induced by TZD. However, this concept is challenged by new studies published in Nature and JCI in June. Both studies consistently suggest that PPARg in macrophages is required for maintenance of insulin sensitivity and energy balance. When PPARg is specifically knocked out in macrophages, mice developed metabolic syndrom and lost response to TZD. See details in attached PDF files.  
 
       Akt is a serine kinase in insulin signaling pathway. The up- and down-stream molecules of Akt are actively studied in several fields, including endocrinology, immunology and cancer biology. The reason is that Akt is also involved in signaling transduction of other growth factors.
Attached include a review for Akt in this issue of Cell.  
 
By Jianping at PBRC/LSU

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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail:
yej@pbrc.edu
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