**4. The importance of KATP channels**

The KATP channels play an integral role in glucose-stimulated insulin secretion by serving as the transducer of a glucose-generated metabolic signal (ie, ATP) to cell electrical activity (membrane depolarization). Thus, like neurons, beta cells are electrically excitable and capa‐ ble of generating Ca2+ action potentials that are important in synchronizing islet cell activity and insulin release. In addition to being signal targets for glucose, KATP channels are the targets for sulfonylureas, which are commonly prescribed oral agents in the treatment of type 2 diabetes. The sulfonylureas, like glucose, induce closure of KATP channels and stim‐ ulate insulin secretion.

The beta-cell KATP channel is a complex octameric unit of 2 different proteins: the sulfony‐ lurea receptor (SUR-1) and an inward rectifier (Kir6.2). The sulfonylurea receptor belongs to a superfamily of ATP-binding cassette proteins and contains the binding site for sulfonylur‐ ea drugs and nucleotides. The inward rectifier represents the K+ conducting pore and is also regulated by ATP. It is interesting that KATP channels are present in other tissues of the body, including heart (SUR-2A/Kir 6.2), smooth muscle (SUR-2B/Kir 6.2), and brain (SUR-1/Kir 6.2). Recently, Mark L. Evans, MD, Yale University Medical School, New Haven, Connecticut, and colleagues have suggested that glucose sensing in the brain during hypo‐ glycemia may be mediated by KATP channels located in brain hypothalamic neurons. Thus, these molecules may also serve as new therapeutic targets for the restoration of impaired hypoglycemia awareness and glucose counterregulation in type 1 diabetes.
