Adult-onset
diabetes, obesity cured in lab mice, scientists report
A new treatment for adult-onset diabetes and obesity developed
by researchers at Indiana University and the German Research Center for
Environmental Health has essentially cured lab animals of obesity, diabetes and
associated lipid abnormalities through improved glucose sensitivity, reduced
appetite and enhanced calorie burning.
In preclinical trials, the new peptide -- a molecular
integration of three gastrointestinal hormones -- lowered blood sugar levels
and reduced body fat beyond all existing drugs, according to the work co-led by
IU Distinguished Professor of Chemistry Richard DiMarchi and Matthias Tschöp,
director of the Institute for Diabetes and Obesity at the German Research
Center for Environmental Health. The new findings were published today in Nature Medicine.
These preclinical results advance the clinical work the team
announced last year that a peptide combining the properties of two endocrine
hormones, GLP-1 and GIP, was an effective treatment for adult-onset diabetes.
This new molecule includes a third hormone activity, glucagon.
In constructing the new single-cell molecules with
triple-hormone action, the researchers found they could reduce body weight in
rodents by about 30 percent, almost twice as much as the GLP-1/GIP double
hormone. The molecules are called triple agonists -- three hormones combined
molecularly that can bind to and activate receptors to produce certain
biological responses.
"This peptide represents the first rationally designed,
fully potent and balanced triple agonist ever achieved in the treatment of any
disease," DiMarchi said. "The benefits of the previously reported
individual co-agonists have been integrated to a single molecule of triple
action that provides unprecedented efficacy to lower body weight and control
metabolism."
In the paper, the team described the new results as
"unparalleled" when compared to earlier tests using the three
hormones alone and together as co-agonists. It is a clear demonstration that
combining GLP-1, GIP and glucagon can produce improved therapeutic effects.
The triple hormone specifically and equally targets three
receptors of GLP-1, GIP and glucagon. GLP-1 and GIP predominantly contribute to
enhancing insulin action and reducing blood glucose.
GLP-1 also curbs appetite,
while glucagon primarily increases the long-term rate at which calories are
burned and improves liver function.
Human clinical trials are being managed by Roche, which also
co-authored the new paper. Inventions associated with this work have been
licensed through the Indiana University Research and Technology Corp. to
Marcadia Biotech Inc., which Roche acquired in 2010.
Additional scientists affiliated with IU and DiMarchi's lab were
co-first author Bin Yang and Joseph Chabenne, Vasily Gelfanov, David Smiley and
Ma Tao.
Story
Source:
The above story is based on materials provided by Indiana University. Note: Materials may be edited for
content and length.
Journal
Reference:
Brian Finan, Bin Yang, Nickki Ottaway, David L Smiley, Tao Ma,
Christoffer Clemmensen, Joe Chabenne, Lianshan Zhang, Kirk M Habegger, Katrin
Fischer, Jonathan E Campbell, Darleen Sandoval, Randy J Seeley, Konrad
Bleicher, Sabine Uhles, William Riboulet, Jürgen Funk, Cornelia Hertel, Sara
Belli, Elena Sebokova, Karin Conde-Knape, Anish Konkar, Daniel J Drucker,
Vasily Gelfanov, Paul T Pfluger, Timo D Müller, Diego Perez-Tilve, Richard D
DiMarchi, Matthias H Tschöp.A rationally designed monomeric peptide
triagonist corrects obesity and diabetes in rodents. Nature Medicine, 2014; DOI: 10.1038/nm.3761
Cite
This Page:
Indiana University. "Adult-onset diabetes, obesity cured in
lab mice, scientists report." Science
Daily, 8 December 2014.
<www.sciencedaily.com/releases/2014/12/141208144404.htm>.