Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets

Electron Microscopic Study of Intercalated Duct Cells in the Chicken Pancreatic Islet and Effects of Tolbutamide Administration

“…Panten et al (1989) reported that the hypo-and hyperglycemic effects of sulfonylurea result from a chang in the permeability of the ATP-dependent K+ channel in the B cell plasma membrane").…”

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

“…The free plasma glibenclamide levels effective in insulin secretion (low nanomolar range) and the drug concentration required for halfmaximal stimulation of insulin release (~ 0.5 nM) from pancreatic islets [16] and insulin-secreting cell lines [5,14] point to the high-affinity binding site as the only functional receptor, the occupancy of which ultimately leads to insulin secretion. The difference in the hypo- Scatchard plots derived from saturation experiments were curve-linear suggesting the existence of both highand low-affinity binding sites in /3-cell tumor membranes, RINm5F cell membranes and RINm5F cells (Fig.…”

“…Specific high-affinity binding sites (for a recent review, see Ashcroft and Ashcroft [11]) have been characterized previously in /3-cell tumor membranes [12][13][14], RINmSF cell membranes and intact RINm5F cells [15], mouse pancreatic islet microsomes [16], hamster insulin-secreting tumor cell (HIT T15) membranes [14,17,18] and intact HIT T15 cells [19]. In fact, a direct correlation has been found for the sulfonylureas studied so far between their dissociation constants for binding to/3-cell membranes and their ability to induce insulin secretion and to lower the blood sugar [5,13,16].…”

“…In fact, a direct correlation has been found for the sulfonylureas studied so far between their dissociation constants for binding to/3-cell membranes and their ability to induce insulin secretion and to lower the blood sugar [5,13,16]. For instance, the second generation sulfonylurea, glibenclamide, is a 1000-fold more potent stimulator of insulin secretion than first generation compounds such as tolbutamide in correlation with the 1000-10 000-fold lower K d value of glibenclamide compared to tolbutamide [5].…”

Sensitivity of Leishmania spp. to Glibenclamide and 4-Aminopiridine: A Tool for the Study of Drug Resistance Development

“…Their complex life cycles, their flexibility and their ability to adapt to diverse environments, where the membrane plays an important role in maintaining the cellular homeostasis, also justify the study of the membrane proteins implicated on structures such as ion channels, pores and membrane transporters (Zilberstein & Shapira 1994). The drug 4-AP has been used extensively for identifying a high variety of voltage-gated K + channels (Castle et al 1989) and GLIB which is a K + ATP channel blocker, has a widespread use to identify K + channels associated with insulin secretion (SchmidAntomarchi et al 1987, Panten et al 1989). More strikingly, the sulphonylurea (GLIB-sensitive) receptor is a member of the ATP-binding cassette or traffic ATP-ase superfamily (Aguilar-Bryan et al 1995) to which the Leishmania P-glycoprotein…”