Sulfonilurea Sulfonylureas act directly on the - cells of the islets of Langerhans to stimulate insulin secretion (Figure 29.7 ). They enter the - cell and bind to the cytosolic surface of the sulfonylurea receptor 1 (SUR1), which forms part of a transmembrane complex with ATP - sensitive Kir6.2 potassium channels (K + ATP channels) (Figure 29.8 ) [50,51] . Binding of a sulfonylurea closes the K + ATP channel, reducing the effl ux of potassium and enabling membrane depolarization. Localized membrane depolarization opens adjacent voltage - dependent L - type calcium channels, increasing calcium infl ux and raising the cytosolic free calcium concentration. This activates calcium - dependent signaling proteins that control the contractility of micotubules and mictrofi laments that mediate the exocytotic release of insulin granules. Preformed insulin granules adjacent to the plasma membrane are promptly released ( “ fi rst phase ” insulin release), followed by a protracted ( “ second phase ” ) period of insulin release that begins about 10 minutes later [52] . The “ second phase ” of insulin release involves translocation of preformed and newly formed insulin granules to the plasma membrane for secretion. Sulfonylureas continue to stimulate insulin release while they are bound to the SUR1 pro- Obat golongan Sulfonilurea menstimulasi sekresi insulin dari sel-sel beta pankreas dengan mekanisme : Sulfonilurea berikatan dengan reseptor sulfonilurea (SUR1) yang membentuk kompleks dengan kanal K+ sensitif-ATP kanal K+ sensitif-ATP tertutup effluks K+ berkurang Terjadi depolarisasi Kanal Ca2+ terbuka influks Ca2+ meningkat konsentrasi Ca2+ tinggi dalam sitosolmeningkatkan kontraktilitas dari mikrotubulus yang mengikat granul insulin meningkatan pelepasan granul insulin (eksositosis)
SulfonilureaSulfonylureas act directly on the - cells of the
islets of Langerhansto stimulate insulin secretion (Figure 29.7 ).
They enter the - celland bind to the cytosolic surface of the
sulfonylurea receptor 1(SUR1), which forms part of a transmembrane
complex withATP - sensitive Kir6.2 potassium channels (K + ATP
channels)(Figure 29.8 ) [50,51] . Binding of a sulfonylurea closes
the K + ATPchannel, reducing the effl ux of potassium and enabling
membranedepolarization. Localized membrane depolarization
opensadjacent voltage - dependent L - type calcium channels,
increasingcalcium infl ux and raising the cytosolic free calcium
concentration.This activates calcium - dependent signaling proteins
thatcontrol the contractility of micotubules and mictrofi laments
thatmediate the exocytotic release of insulin granules.
Preformedinsulin granules adjacent to the plasma membrane are
promptlyreleased ( fi rst phase insulin release), followed by a
protracted( second phase ) period of insulin release that begins
about 10minutes later [52] . The second phase of insulin release
involvestranslocation of preformed and newly formed insulin
granules tothe plasma membrane for secretion. Sulfonylureas
continue tostimulate insulin release while they are bound to the
SUR1 pro-
Obat golongan Sulfonilurea menstimulasi sekresi insulin dari
sel-sel beta pankreas dengan mekanisme :Sulfonilurea berikatan
dengan reseptor sulfonilurea (SUR1) yang membentuk kompleks dengan
kanal K+ sensitif-ATP kanal K+ sensitif-ATP tertutup effluks K+
berkurang Terjadi depolarisasi Kanal Ca2+ terbuka influks Ca2+
meningkat konsentrasi Ca2+ tinggi dalam sitosolmeningkatkan
kontraktilitas dari mikrotubulus yang mengikat granul insulin
meningkatan pelepasan granul insulin (eksositosis)
Contoh Obat dan Dosis
Efek sampingHipoglikemia terutama pada pasien dengan
insufisiensi ginjal dan hati, dimana ekskresi obat terhambat dan
dapat terakumulasi(Richard A Harvey, Lippincotts Illustrated
Reviews : Pharmacology 4th Ed, Halaman 343)Hiponatremia (
