FGF-21 finds itself as a new therapy for type 2 diabetes
Members of the fibroblast growth factor (FGF) family of proteins play many regulatory roles in several tissues. FGF-21 is a novel member of the FGF family, but its biological role was not known. In a study appearing online on May 2 in advance of the print publication of the June issue of the Journal of Clinical Investigation, Alexei Kharitonenkov and colleagues from Lilly Research Laboratories show that FGF-21 may be a new therapeutic treatment for Diabetes Mellitus.
The researchers show that FGF-21 regulates glucose uptake in human fat cells. Moreover, therapeutic administration of FGF-21 decreased plasma glucose levels and triglycerides to near normal levels in multiple mouse models of type 2 diabetes. FGF-21, when overexpressed, protected animals from diet-induced obesity. These results define a functional role for FGF-21 in vivo and provide evidence that FGF-21 can lower glucose and triglyceride levels in diabetic animals.
TITLE: FGF-21 as a novel metabolic regulator
AUTHOR CONTACT:
Alexei Kharitonenkov
Lilly Research Laboratories, Indianapolis, IN USA
Phone: (317) 276-0091; Fax: (317) 277-2934; E-mail: a.kharch@lilly.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=23606
PHYSIOLOGY
Breaking down barriers in bacterial infection
Endothelial cells separate the blood from the tissues of the body and form barriers for protection. Death of these cells can allow for bacterial invasion and infection. In a study appearing online on May 2 in advance of the print publication of the June issue of the Journal of Clinical Investigation, Joerg Weber and colleagues from Charite describe the ability of Gram-positive Streptococcus pneumoniae, a powerful pathogen, to induce two functionally and morphologically distinct forms of programmed cell death in endothelial cells. One pathway is classical apoptosis and the other is an apoptotic-like pathway mediated by bacterial toxins. This study advances our understanding of bacteria-induced cell death and provides insight into the acute and persistent phases of cell damage during invasive infections like sepsis and meningitis.
TITLE: Bacterial programmed cell death of cerebral endothelial cells: dual death pathways
AUTHOR CONTACT:
Joerg Weber
Charite - Universitaetsmedizin Berlin, Germany
Phone: +49 30 450 560104; Fax: +49 30 450 560942; E-mail: joerg.weber@charite.de
View the PDF of this article at: https://www.the-jci.org/article.php?id=23223
PHYSIOLOGY
Asthma mechanisms down to a T
Asthma is a chronic inflammation of the airways that causes remodeling of the airway architecture and increased airway smooth muscle mass. In a study appearing online on May 2 in advance of the print publication of the June issue of the Journal of Clinical Investigation, James Martin, Elizabeth Fixman and colleagues from McGill University study the role of immune T cells in the structural changes in the airway associated with asthma.
The authors use a rodent model of experimental asthma to show that antigen-specific CD4+ T cells infiltrate the airway wall, where they may act on airway smooth muscle to regulate muscle cell proliferation and death. This increases the amount of smooth muscle in the airways, an important feature of asthma. The results offer a novel role for antigen-specific CD4+ T cells in airway remodeling in experimental asthma and insight into the disease mechanisms of asthma.
TITLE: Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma
AUTHOR CONTACT:
James Martin
McGill University, Montreal, Canada
Phone: (514) 398-3864; Fax: (514) 398-7483; E-mail: james.martin@mcgill.ca
View the PDF of this article at: https://www.the-jci.org/article.php?id=19711
PHYSIOLOGY
Building new blood vessels
The formation of new blood vessels, neovascularization, plays a role in development and in healing of injured tissues. In a study appearing online on May 2 in advance of the print publication of the June issue of the Journal of Clinical Investigation, Judy Varner and colleagues from UCSD describe new work revealing that developing blood vessels require direct adhesion of endothelial cells and pericytes, small supporting cells surrounding blood vessels.
The authors identify the molecules on each cell (a receptor-ligand pair called VLA4 and VCAM) that promotes this adhesion and neovascularization. Blocking this interaction inhibits neovascularization. This work identifies a new concept in the basic process of blood vessel formation.
TITLE: Integrin alpha4beta1-VCAM mediated adhesion between endothelial and mural cells is required for blood vessel maturation
AUTHOR CONTACT:
Judith A. Varner
University of California, San Diego, La Jolla, CA USA
Phone: (858) 822-0086; Fax: (858) 822-1325; E-mail: jvarner@ucsd.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=23445
ONCOLOGY
How normal B cells become leukemic cells
B cell chronic lymphocytic leukemia (CLL) is a disease in which outcome can be at least partially predicted by whether the patient has mutations in the B cell receptor (BCR) or not, the latter of which predicts the more favorable clinical outcome. In a study appearing online on May 2 in advance of the print publication of the June issue of the Journal of Clinical Investigation, Eric Meffre and colleagues from the Hospital for Special Surgery determine the role of antibody reactivity and the impact of mutations on CLL antibody specificity.
The authors cloned and expressed antibodies from M- and UM-CLL B cells and found that UM-CLL B cells expressed highly reactive antibodies whereas most M-CLL B cells did not. They conclude that both UM-CLLs and M-CLLs actually originate from common B cell precursors and that the mutations play an important role in the development of the disease by altering original BCR autoreactivity. These results further our understanding of how normal B cells become CLL cells.
TITLE: Unmutated and mutated chronic lymphocytic leukemia derive from self-reactive B cell precursors despite expressing different antibody reactivity
AUTHOR CONTACT:
Eric Meffre
Hospital for Special Surgery, New York, NY USA
Phone: (212) 774-2347; Fax: (212) 717-1192; E-mail: meffree@hss.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24387
Journal
Journal of Clinical Investigation