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
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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.