Metabolic Syndromes

Biography

Biography: Hussein Nori Rubaiy

Abstract

ATP-sensitive potassium (KATP) channels, which are unique among potassium channels are ubiquitously expressed and link metabolic state to electrical excitability. KATP channels are crucial in the regulation of glucose-induced insulin secretion. In pancreatic β-cells, an increase in ATP/ADP ratio, which is generated by glucose uptake and metabolism, closes the KATP channels to elicit membrane depolarization, calcium influx and a secretion of insulin, the primary hormone of glucose homeostasis. KATP channels are composed of a hetero-octamer of two subunits types, a pore forming Kir6 subunit, which is a member of the inwardly rectifying potassium channel family and a sulfonylurea receptor (SUR), a regulatory subunit, which is a member of the ATP binding cassette family of proteins. In response to nucleotides and pharmaceutical agonists and antagonists, SUR allosterically regulates KATP channel gating. More than three decades after the discovery of KATP channels, the transduction pathways for allosteric communication, which make the functional link between the pore forming Kir6 and the regulatory SUR subunits of KATP channels, remain poorly understood. A crystal structure of KATP channels will clarify the allosteric communications and the structure-function relationship between KATP channels subunits, which induce the conformational changes and the channel gating.