|
||
| |||||||
|
GSK-3 inhibition as a strategy for improving glucose handling in diabetes Regular readers of TherapeuticAdvances will know that LeadDiscovery has recently responded to the massive upsurge in interest in glycogen synthase kinase-3 (GSK-3) by publishing a report overviewing the therapeutic and pharmaceutical potential of this enzyme. Data is now emerging at a rate of over 400 publications/year, 10-times that 5 years ago. This research supports the development of GSK-3 inhibitors for treatment of many diseases including Alzheimer's disease, stroke & bipolar disorder, although perhaps the greatest research surround its potential in the treatment of diabetes. GSK-3 inhibitors may increase insulin sensitivity and possibly insulin secretion however the most convincing proof of concept surrounds the improvement of glucose disposal. Glycogen levels are markedly reduced in liver or muscle cells of patients with type 2 diabetes, suggesting that impaired glycogen synthesis may contribute to development of hyperglycemia. Glycogen synthase appears to be the rate-limiting step for glycogen synthesis, at least in the liver, and it is therefore reasonable to assume that a defect in GSK-3 regulation might be associated with a failure of insulin to activate glycogen synthase. A recent study by Cline et al. suggests that this is indeed the case. These authors report that GSK-3 inhibition improved glucose handling in Zucker diabetic fatty rats, lowering fasting hyperglycemia. Improved glucose disposal was mostly attributed to an increase in liver glycogen synthesis correlating with an increase in glycogen synthase seen under in vivo conditions. These breakthrough studies present for the first time in vivo evidence in a model of diabetes that GSK-3 inhibition can improve glucose handling and as such offer excellent proof of concept for the development of this therapeutic class. December, 2002
Adapted from Cline et al, Diabetes 2002 Oct;51(10):2903-10 Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk Projects such as these are overviewed in full DiscoveryDossiers. LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
|
| ||||||||
