Diabetes affects almost 400 million people worldwide. One of the hallmarks of this disease is a loss of pancreatic β cells, which secrete insulin. In many patients the reduction of β cells is associated an accumulation of a toxic form of a protein produced by β cells, known as islet amyloid polypeptide. There are no therapies or treatment available to restore the β cell populations or function.
Three new studies in Journal of Clinical Investigation identify a pathway that protects β cells from the toxic form of islet amyloid polypeptide. Using animal models, all three groups found that a functional autophagy system, which acts to degrade dysfunctional cellular components, prevents toxic accumulation of islet amyloid polypeptide. Animals that expressed the human form of islet amyloid polypeptide, but produced β cells that were autophagy deficient, developed overt diabetes.
In the accompanying Commentary, Dhananjay Gupta and Jack L. Leahy suggest that enhancing autophagy in pre-diabetic patients has potential to prevent or delay the onset of diabetes.
Title
Autophagy defends pancreatic β cells from human islet amyloid polypeptide-induced toxicity
Author Contact
Peter Butler
UCLA, Los Angeles, USA
Phone: 310 206 7312
E-mail: pbutler@mednet.ucla.edu
View this article at: http://www.jci.org/articles/view/71981?key=963d35a35b227e4645ad
Human IAPP–induced pancreatic β cell toxicity and its regulation by autophagy
Yoshio Fujitani
Juntendo University Graduate School of Medicine
Tokyo, Japan
Phone: 81-3-5802-1579
E-mail: fujitani@juntendo.ac.jp
View this article at: http://www.jci.org/articles/view/69866?key=654d9fc3fdf47dd4dc4c
Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes
Myung-Shik Lee
Samsung Medical Center
Seoul, Korea
Phone: 82-2-3410-3436
E-mail: mslee0923@skku.edu
View this article at: http://www.jci.org/articles/view/69625?key=68ee3c30b471e1685dd4
Accompanying Commentary
Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification?
Jack L. Leahy
University of Vermont
Colchester, VT, USA
Phone: 802-656-0835
Fax: 802-656-8031
E-mail: jleahy@uvm.edu
View this article at: http://www.jci.org/articles/view/77506?key=99364d6f41ede593769e
Journal of Clinical Investigation