Where do beta cells come from? A new method of studying human islet cell development

Beta Cells within Single Human Islets Originate from Multiple Progenitors
Original source: PLoS ONE 3(10): e3559
Authors: Raphaël Scharfmann, Xiangwei Xiao, Harry Heimberg, Jacques Mallet, Philippe Ravassard (corresponding author)
Publication date: October 29, 2008
DOI (digital document ID): 10.1371/journal.pone.0003559
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Beta cells are the insulin-producing cells within the Islets of Langerhans, located in the pancreas. Most of our understanding of how beta cells develop is based on studies of mice and rats. The authors' goal was to develop a model to transfer genes into developing human pancreas cells and to see if the gene transfer worked by looking at how the cells multiplied and specialized.

Pancreas cells were removed from human fetuses and tagged with a specific virus tag, called a replication-defective lentivirus, and islet-cell specific DNA from human pancreas tissue. These tissues were were grafted onto mice whose were treated to not reject the transplant. This technique had previously been tested to make sure it would be able to grow new human cells from the grafted cell, and that the tags would only show up on new cells grown from the grafted tissue. The tagged cells were allowed to grow and differentiate, to create new islet bodies. The new human islets contained both tagged and untagged cells, suggesting that islet cell growth is more than a simple matter of cell multiplication.

Reliability:
The authors are professionals in the fields of medicine, medical research, and diabetes research, and associated with accredited institutions. The research was published in a peer-reviewed journal. The article explained the technical details of tissue preparation and growth. The research was funded, but not directed, by grants from a combination of diabetes-research foundations.

Practical Applications:
This investigation falls under the heading of primary research -- how islet cells form and develop -- which is considered one of the key issues involved in understanding and curing diabetes.

Ethics note:
Studies using human cells -- such as the fetus cells and human pancreas cells used in this experiment -- must meet certain ethical standards. In this case, the fetuses came from pregnancies the parents chose to abort between the 9th and 11th weeks of pregnancy, and the cells were taken with the informed consent of the mothers. The human pancreas cells were taken from a pancreas that had been lawfully donated for transplantation and research.

This synopsis was based on the entire article.

Investigating Insulin Resistance in the Liver

Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance
Authors: Markus Hafner, Anton Schmitz, Imke Grüne, Seergazhi G. Srivatsan, Bianca Paul, Waldemar Kolanus, Thomas Quast, Elisabeth Kremmer, Inga Bauer and Michael Famulok
Original source: Nature Volume 444, pp. 941-944
Publication date: 14 December 2006
DOI (digital document ID): doi:10.1038/nature05415
Requires subscription? For complete article
Publicly-available abstract: Yes

Synopsis:
G proteins regulate biochemical "switches" in all living systems. They are switched on and off by chemicals called "guanine nucleotide exchange factors" or GEFs. Finding chemicals which increase or inhibit GEFs may be useful both to find out how GEFs work and to treat diseases in which the G proteins are affected.

A specific class of GEFs called "cytohesins" includes some GEFs that are associated with insulin production and signalling. The investigators found that in humans, a chemical called "SecinH3" might inhibit the cytohesins associated with insulin signalling. To test this theory, mice were treated with SecinH3 and observed to determine whether or not they showed increased signs of insulin resistance.

The mice exhibited increased glucose production, reduced glycogen storage and glycogen-to-glucose conversion, a reduced ability to metabolize fatty acids and ketones, and increased plasma insulin. These are all symptoms of insulin resistance, suggesting that increased levels of SecinH3, and/or decreased activity of cytohesins, may be responsible for insulin resistance.

The importance of this finding is that insulin resistance is one of the first signs of Type 2 diabetes.

Reliability:
The initial hypothesis was based on the isolation of SecinH3 and its effects in isolated human liver tissue, so even though this experiment took place in mice, it has a good probability of being directly transferrable to people. The article was published in a peer-reviewed journal, and the authors are professional researchers in biochemistry and immunology.
This leads to high confidence in the results.

Practical applications:
This research is still very early on in the process of developing new treatments for insulin resistance and Type 2 Diabetes.

This synopsis was based on the abstract only.