TY - JOUR
T1 - Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus
AU - Lotfy, Mohamed
AU - Singh, Jaipaul
AU - Kalász, Huba
AU - Tekes, Kornelia
AU - Adeghate, Ernest
PY - 2011
Y1 - 2011
N2 - Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.
AB - Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.
KW - DPP-4 inhibitors
KW - Incretins
KW - Medicinal chemistry
KW - Type 2 diabetes
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U2 - 10.2174/1874104501105010082
DO - 10.2174/1874104501105010082
M3 - Review article
C2 - 21966329
AN - SCOPUS:80455131061
SN - 1874-1045
VL - 5
SP - 82
EP - 92
JO - Open Medicinal Chemistry Journal
JF - Open Medicinal Chemistry Journal
IS - SPEC. ISSUE 2
ER -