Modulation of Glucokinase Regulatory Protein: A Double-Edged Sword?
The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be...
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| Veröffentlicht in: | Trends in molecular medicine 2015-10, Vol.21 (10), p.583-594 |
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| creator | Brouwers, Martijn C.G.J Jacobs, Chantal Bast, Aalt Stehouwer, Coen D.A Schaper, Nicolaas C |
| description | The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be introduced to T2DM patients. Recently, genome-wide association studies (GWASs) have shown that variants in the gene encoding GKRP protect against T2DM and kidney disease but predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These genetic data, together with previous experience with systemic and hepatospecific glucokinase activators, provide insight into the anticipated efficacy and safety of small-molecule disruptors in humans. Interestingly, they suggest that the opposite – enhanced GKRP–glucokinase binding – could be beneficial in selected patients. |
| doi_str_mv | 10.1016/j.molmed.2015.08.004 |
| format | Article |
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| subjects | Adaptor Proteins, Signal Transducing - antagonists & inhibitors Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Animals Carrier Proteins - metabolism Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - therapy Genetic Predisposition to Disease Glucokinase - metabolism Humans Hypoglycemic Agents - pharmacology Metabolomics Mice Pathology |
| title | Modulation of Glucokinase Regulatory Protein: A Double-Edged Sword? |
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