Present status of clinical deployment of glucokinase activators

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Present status of clinical deployment of glucokinase activators

Glucokinase is one of four members of the hexokinase family of enzymes. Its expression is limited to the major organs (such as the pancreas, liver, brain and the gastrointestinal tract) that are thought to have an integrated role in glucose sensing. In the liver, phosphorylation of glucose by glucokinase promotes glycogen synthesis, whereas in the β-cells, it results in insulin release. Studies...

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Glucokinase Activators for Diabetes Therapy

Type 2 diabetes is characterized by elevated blood glucose levels resulting from a pancreatic b-cell secretory insufficiency combined with insulin resistance, most significantly manifested in skeletal muscle and liver (1). If untreated, diabetic complications develop that cause loss of vision, peripheral neuropathy, impaired kidney function, heart disease, and stroke. The disease has a polygeni...

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Comparative Docking Assessment of Glucokinase Interactions with its Allosteric Activators

Glucokinase (GK) is expressed in multiple organs and plays a key role in hepatic glucose metabolism and pancreatic insulin secretion. GK could indeed serve as pacemaker of glycolysis and could be an attractive target for type 2 diabetes (T2D). The recent preclinical data of first GK activator RO-28-1675 has opened up a new field of GK activation as a powerful tool in T2D therapies. The GK allos...

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Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics

The glucose-phosphorylating enzyme glucokinase, a promising target for developing new antidiabetic agents, was identified through the combined efforts of basic research and human biochemical genetics. Allosteric glucokinase activators (GKAs) were discovered by high-throughput screening of a large compound library and first reported in 2003. GKAs stimulate insulin release and glucose metabolism ...

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ژورنال

عنوان ژورنال: Journal of Diabetes Investigation

سال: 2014

ISSN: 2040-1116,2040-1124

DOI: 10.1111/jdi.12294