| Glycogen synthase kinase 3: more than a namesake. | |
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MedLine Citation:
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PMID: 19366350 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, tau protein and beta catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. GSK3 negatively regulates insulin-mediated glycogen synthesis and glucose homeostasis, and increased expression and activity of GSK3 has been reported in type II diabetics and obese animal models. Consequently, inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in vitro and in animal models. However, inhibition of GSK3 poses a challenge as achieving selectivity of an over achieving kinase involved in various pathways with multiple substrates may lead to side effects and toxicity. The primary concern is developing inhibitors of GSK3 that are anti-diabetic but do not lead to up-regulation of oncogenes. The focus of this review is the recent advances and the challenges surrounding GSK3 as an anti-diabetic therapeutic target. |
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Authors:
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Geetha Vani Rayasam; Vamshi Krishna Tulasi; Reena Sodhi; Joseph Alex Davis; Abhijit Ray |
Publication Detail:
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Type: Journal Article; Review Date: 2009-03-04 |
Journal Detail:
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Title: British journal of pharmacology Volume: 156 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-04-15 Completed Date: 2009-07-20 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 885-98 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Research & Development (R&D III), Ranbaxy Research Labs, Gurgaon, Haryana, India. geeta.rayasam@ranbaxy.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Transformation, Neoplastic / metabolism, pathology Diabetes Mellitus, Type 2 / drug therapy, enzymology Glucose / physiology Glycogen Synthase / metabolism Glycogen Synthase Kinase 3 / antagonists & inhibitors, physiology* Homeostasis Humans Hypoglycemic Agents / pharmacology, therapeutic use Insulin / physiology Pancreas / enzymology Signal Transduction Wnt Proteins / physiology |
| Chemical | |
Reg. No./Substance:
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0/Hypoglycemic Agents; 0/Wnt Proteins; 11061-68-0/Insulin; 50-99-7/Glucose; EC 2.4.1.11/Glycogen Synthase; EC 2.7.1.37/glycogen synthase kinase 3 alpha; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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