Wie ist der Unterricht in der Geschichte auf den höheren Lehranstalten zu handhaben und seinem Stoffe nach auf die einzelnen Klassen zu verteilen, damit die Geschichte der neuesten Zeit und die Kulturgeschichte in ausreichendem Maße Berücksichtigung finden? : drei Gutachten

G. Lohmeyer ; Rühle ; E. Pante

Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells.

The influence of the hypoglycemic drugs tolbutamide, meglitinide, glipizide and glibenclamide on ATP-dependent K+ currents of mouse pancreatic B-cells was studied using the whole-cell configuration of the patch-clamp technique. In the absence of albumin, tolbutamide blocked the currents half maximally at 4.1 μmol/l. In the presence of 2 mg/ml albumin half maximal inhibition of the currents was observed at 2.1 μmol/l meglitinide, 6.4 nmol/l glipizide and 4.0 nmol/1 glibenclamide. The hyperglycemic sulfonamide diazoxide opened ATP-dependent K+channels. Half maximally effective concentrations of diazoxide were 20 μmol/l with 0.3 mmol/1 ATPand102 μmol/l with 1 mmol/1 ATP in the recording pipette. Thus, the action of diazoxide was dependent on the presence of ATP in the recording pipette. The free concentrations of the drugs which influenced ATP-dependent K+ currents were comparable with the free plasma concentrations in humans and the free concentrations which affected insulin secretion in vitro. The results support the view that the target for the actions of sulfonylureas and of diazoxide is the ATP-dependent K+ channel of the pancreatic B-cell or a structure closely related to this channel