Sulfonylurea and non-sulfonylurea hypoglycemic agents: pharmachological properties and tissue selectivity

Abstract

ATP-sensitive K+ (KATP) channels play many important roles in cellular functions, including control of membrane excitability of skeletal muscle and neurons, K+ recycling in renal epithelia, cytoprotection in cardiac ischemia, and insulin secretion from pancreatic β-cells. KATP channels are composed of pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits. Kir6.2 or Kir6.1 subunits conjoined with a SUR subunit constitute the various tissue-specific KATP channels with distinct pharmacological properties. Both sulfonylureas and non-sulfonylurea hypoglycemic agents are used in treatment of type 2 diabetes mellitus. While the sulfonylurea receptor (SUR) is the target molecule of all of these hypoglycemic agents, the binding sites differ according to the moiety containing in the agent, and alter the pharmachological properties. In addition, chronic exposure of pancreatic β-cells to the various agents affects the agent-specific sensitivities differently.Here we distinguish differences in pharmacological profile among the various hypoglycemic agents that reflect their chemical composition. We also suggest possible risk in the use of certain hypoglycemic agents in patients with ischemic heart disease.