Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Pancreatic Chromatin Manipulation Generates New Insulin Producing Cells

By BiotechDaily International staff writers
Posted on 03 Mar 2013
Image: Treatment of human islets with the histone methyltransferase inhibitor Adox results in co-localization of the beta-cell specific transcription factor PDX1 (white) in a substantial subpopulation of glucagon-positive cells (red), indicating partial endocrine cell-fate conversion (Photo courtesy of  Nuria Bramswig, Perelman School of Medicine, University of Pennsylvania).
Image: Treatment of human islets with the histone methyltransferase inhibitor Adox results in co-localization of the beta-cell specific transcription factor PDX1 (white) in a substantial subpopulation of glucagon-positive cells (red), indicating partial endocrine cell-fate conversion (Photo courtesy of Nuria Bramswig, Perelman School of Medicine, University of Pennsylvania).
Genomic researchers have created insulin-producing pancreatic beta cells through the selective enzymatic manipulation of the chromatin of glucagon-producing alpha cells.

Glucagon is a hormone secreted by alpha cells in the pancreas that raises blood glucose levels. Its effect is opposite that of beta cell insulin, which lowers blood glucose levels. The pancreas releases glucagon when glucose levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. High blood glucose levels stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin-dependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels at a stable level.

Loss of beta cells and subsequent lack of insulin causes diabetes. One theoretical approach to correcting this problem is to convert some other cell type, such as alpha cells, into beta cells. To this end, investigators at the University of Pennsylvania (Philadelphia, USA) launched an in-depth study of the alpha and beta cell genomes.

They used ChIP sequencing and RNA sequencing analysis, to determine the epigenetic and transcriptional landscape of human pancreatic alpha, beta, and exocrine cells. ChIP sequencing is a method used to demonstrate the association between transcription factors or other DNA-binding proteins and specific regions of genomic DNA. Chromatin is isolated from preparations of nuclei, chemically cross-linked, and sheared to provide short fragments. Antibodies are used to immunoprecipitate the specific DNA-binding protein and with it, the fragment of DNA to which it is bound. Polymerase chain reaction (PCR) is then used to identify the presence of specific DNA fragments.

The investigators reported in the February 22, 2013, online edition of the Journal of Clinical Investigation that compared with exocrine and beta cells, differentiated alpha cells exhibited many more genes bivalently marked by activating and repressing histone modifications. Thousands of these genes were in a monovalent state in beta cells, carrying only the activating or repressing mark. Epigenomic findings suggested that alpha to beta cell reprogramming could be promoted by manipulating the histone methylation signature of human pancreatic islets.

Treatment of cultured pancreatic islets with a histone methyltransferase inhibitor led to co-localization of both glucagon and insulin and glucagon and insulin promoter factor 1 (PDX1) in human islets and co-localization of both glucagon and insulin in mouse islets. Therefore, mammalian pancreatic islet cells displayed cell-type–specific epigenomic plasticity, suggesting that epigenomic manipulation could provide a path to cell reprogramming and novel cell replacement-based therapies for diabetes.

"To some extent human alpha cells appear to be in a "plastic" epigenetic state," said senior author Dr. Klaus H. Kaestner, professor of genetics at the University of Pennsylvania. "We reasoned we might use that to reprogram alpha cells towards the beta-cell phenotype to produce these much-needed insulin-producing cells. We treated human islet cells with a chemical that inhibits a protein that puts methyl chemical groups on histones, which - among many other effects - leads to removal of some histone modifications that affect gene expression. We then found a high frequency of alpha cells that expressed beta-cell markers, and even produced some insulin, after drug treatment."

"This would be a win-win situation for diabetics," said Dr. Kaestner. "They would have more insulin-producing beta cells and there would be fewer glucagon-producing alpha cells."

Related Links:

University of Pennsylvania



Channels

Drug Discovery

view channel

Curcumin Used to Treat Alzheimer’s Disease

Curcumin, a natural substance found in the spice turmeric, has been used by many Asian cultures for centuries. Now, new research suggests that a close chemical analog of curcumin has properties that may make it useful as a treatment for Alzheimer’s disease. “Curcumin has demonstrated ability to enter the brain, bind... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.