Recent advances in glucokinase activators for the treatment of type 2 diabetes.
Glucokinase is a member of the hexokinase family of enzymes that are responsible for the phosphorylation of glucose to glucose-6-phosphate for further utilization in cells. The enzyme plays a key role in glucose homeostasis. Phosphorylation of glucose by glucokinase in the liver promotes glycogen synthesis, while in the beta-cell it results in insulin release. Activators of glucokinase increase the sensitivity of the enzyme to glucose, leading to increased insulin secretion and liver glycogen synthesis and a decrease in liver glucose output. Thus, small molecule glucokinase activators have been demonstrated to be effective glucose-lowering agents in animal models of type 2 diabetes and have advanced into clinical studies.
Pal
Manojit
M
New Drug Discovery, Matrix Laboratories Limited, Anrich Industrial Estate, Bollaram, Jinnaram Mandal, Medak District, Andhra Pradesh 502 325, India. manojitpal@rediffmail.com
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use*; D005941:Glucokinase / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation
D001786:Blood Glucose; D020536:Enzyme Activators; D007004:Hypoglycemic Agents; D005941:Glucokinase; D005947:Glucose