Treating diabetes today: a matter of selectivity of sulphonylureas
| Autor: | Harumi Takahashi, Tadao Shibasaki, Toshimasa Takahashi, Susumu Seino |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
endocrine system
medicine.medical_specialty Receptors Drug Endocrinology Diabetes and Metabolism medicine.medical_treatment Telomere-Binding Proteins Incretin Biology Sulfonylurea Receptors Exocytosis Shelterin Complex Endocrinology KATP Channels Insulin-Secreting Cells Internal medicine Insulin Secretion Cyclic AMP Internal Medicine medicine Guanine Nucleotide Exchange Factors Humans Hypoglycemic Agents Insulin Gliclazide Potassium Channels Inwardly Rectifying Receptor Type 2 Diabetes Mellitus Potassium channel Sulfonylurea Compounds Diabetes Mellitus Type 2 Sulfonylurea receptor ATP-Binding Cassette Transporters hormones hormone substitutes and hormone antagonists Signal Transduction medicine.drug |
| Zdroj: | Diabetes, Obesity and Metabolism. 14:9-13 |
| ISSN: | 1462-8902 |
| DOI: | 10.1111/j.1463-1326.2011.01507.x |
| Popis: | It is well known that sulphonylureas (SUs), commonly used in the treatment of type 2 diabetes mellitus, stimulate insulin secretion by closing ATP-sensitive K(+) (K(ATP) ) channels in pancreatic β-cells by binding to the SU receptor SUR1. SUs are now known also to activate cAMP sensor Epac2 (cAMP-GEFII) to Rap1 signalling, which promotes insulin granule exocytosis. For SUs to exert their full effects in insulin secretion, they are required to activate Epac2 as well as to inhibit the β-cell K(ATP) channels. As Epac2 is also necessary for potentiation of glucose-induced insulin secretion by cAMP-increasing agents, such as incretin, Epac2 is a target of both cAMP and SUs. The distinct effects of various SUs appear to be because of their different actions on Epac2/Rap1 signalling as well as K(ATP) channels. Differently from other SUs, gliclazide is unique in that it is specific for β-cell K(ATP) channel and does not activate Epac2. |
| Databáze: | OpenAIRE |
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