Figure 1

Genetic defects in the beta cell leading to hyperinsulinism. Inthe pancreatic beta cell, ATP production from fuel metabolism leads toinhibition and closure of ATP-sensitive potassium channels, whichtriggers membrane depolarization and opening of voltage-dependentcalcium channels. The resulting increase in cytosolic calcium triggersinsulin secretion. Defects in this pathway can result inhyperinsulinism. The known protein defects are depicted in bold italics.Five are inactivating mutations: SUR-1 (sulfonylurea receptor), Kir6.2(potassium channel), SCHAD (short-chain 3-OH acyl-CoA dehydrogenase),UCP2 (uncoupling protein 2), HNF-4α (hepatic nuclear transcriptionfactor 4α), and HNF-1α (hepatic nuclear transcription factor1α). The last 2 are transcription factors and are not depicted inthe figure. Three are activating mutations: GK (glucokinase), GDH(glutamate dehydrogenase), MCT-1 (monocarboxylate transporter 1).Positive effects are shown by a plus arrow; negative effects by a minusarrow. Dashed arrows denote multiple steps in a pathway. G6P =glucose-6-phosphate, ATP = adenosine triphosphate, ADP = adenosinediphosphate.