Diabetes mellitus is a worldwide impacting disorder and the ratio through which the number of diabetic patients had increased worldwide, puts medical professionals to serious stress for its effective management. Due to its polygenic origin and involvement of multiple genes to its pathophysiology, leads to understanding of this ailment more complex. It seems that current interventions, such as dietary changes, life style changes and drug therapy such as oral hypoglycaemics and insulin, are unable to halt the trend. There are various novel and emerging targets on which the researchers are paying attention to combat with this ailment successfully. Human glucokinase (GK) enzyme is one of these novel and emerging targets for management of diabetes. Its availability in the pancreas and liver cells makes this target more lucrative. GK's presence in the pancreatic and hepatic cells plays a very important function for the management of glucose homoeostasis. Small molecules that activate GK allosterically provide an alternative strategy for restoring/improving glycaemic regulation, especially in type 2 diabetic patients. Although after enduring many setbacks in the development of the GK activators, interest has been renewed especially due to introduction of novel dual acting GK activator dorzagliatin, and a novel hepato-selective GK activator, TTP399. This review article has been formulated to discuss importance of GK in glucose homeostasis, recent updates on small molecules of GK activators, clinical status of GK activators and challenges in development of GK activators.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167346 | PMC |
| http://dx.doi.org/10.1007/s40200-022-01019-x | DOI Listing |
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Article Synopsis
- Diabetes is a significant global health issue that involves high healthcare costs and complex treatments, leading to the search for new medication options due to the side effects of current therapies.
- Glucokinase (GK) plays a crucial role in regulating blood sugar levels and has unique properties that make it a good target for type-2 diabetes treatment; glucokinase activators (GKAs) can enhance GK activity, but safety concerns persist with existing options.
- A study developed a new type of GKA using peptide-based compounds with unique amino acids, discovering three promising peptides that increase GK activity significantly; machine learning techniques were also employed to predict their effectiveness.
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