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Diabetes: Symptoms, Treatment and Latest Research
#13
Let us first understand the basis of the research that driven the invention of the drug that actually 'Mimics Exercise' and helps controlling blood sugar levels and hence diabetes:

Quote:When ever you exercise, your body cells get depleted of energy and hence the glucose uptake into the cells from blood takes place and ATP (energy) is produced. So, the researchers from University of Southampton (England) ended up finding a pathway (alternative to the conventional one) to activate an important protein (enzyme) required for glucose uptake by the cells, thereby successfully mimicking the effects of exercise (some, if not all effects though).

This research was published in the Cell journal on July 23rd 2015. They have named the drug as "Compound 14". Following is a graphical abstract to their research followed by the 'verbatim abstract from the journal'. You may read the full article in PubMed or Cell.
[Image: fx1.jpg]

Note the following is taken exactly from the original article:

Quote:Summary

5-Aminoimidazole-4-carboxamide ribonucleotide (known as ZMP) is a metabolite produced in de novo purine biosynthesis and histidine biosynthesis, but only utilized in the cell by a homodimeric bifunctional enzyme (called ATIC) that catalyzes the last two steps of de novo purine biosynthesis. ZMP is known to act as an allosteric activator of the cellular energy sensor adenosine monophosphate-activated protein kinase (AMPK), when exogenously administered as the corresponding cell-permeable ribonucleoside. Here, we demonstrate that endogenous ZMP, produced by the aforementioned metabolic pathways, is also capable of activating AMPK. Using an inhibitor of ATIC homodimerization to block the ninth step of de novo purine biosynthesis, we demonstrate that the subsequent increase in endogenous ZMP activates AMPK and its downstream signaling pathways. We go on to illustrate the viability of using this approach to AMPK activation as a therapeutic strategy with an in vivo mouse model for metabolic disorders.

Highlights

•AICAR transformylase is targeted in cells with an ATIC homodimerization inhibitor
•The resulting increase in endogenous ZMP is sufficient to activate AMPK
•Downstream AMPK signaling is also activated, significantly altering cell metabolism
•A mouse model of metabolic syndrome is used to show therapeutic viability

The original article is an open access article available at: http://www.cell.com/chemistry-biology/fu...%2900234-3
Sunil Nagpal
MS(Research) Scholar, IIT Delhi (Alumnus)
Advisor for the Biotech Students portal (BiotechStudents.com)
Computational Researcher in BioSciences at a leading MNC


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Drug that Mimics Exercise for Diabetes Control - by SunilNagpal - 08-22-2015, 10:02 PM
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