title: Different effects of tolbutamide and diazoxide in alpha, beta-, and delta-cells within intact islets of Langerhans.
abstract: Interaction between the different types of cells within the islet of Langerhans is vital for adequate control of insulin release. Once insulin secretion becomes defective, as in type 2 diabetes, the most useful drugs to increase insulin release are sulfonylureas. It is well-known that sulfonylureas block K(ATP) channels, which results in depolarization of the membrane that provokes calcium influx and increases intracellular calcium concentration ([Ca2+]i), which thereby triggers insulin secretion. The sulfonamide diazoxide produces the opposite effect: it activates K(ATP) channels, resulting in a decreased insulin secretion. Despite such evidence, little is known about the effect of sulfonylureas and sulfonamides in non-beta-cells of the islet of Langerhans. In this article, we describe the effects of tolbutamide and diazoxide on [Ca2+]i in alpha-, beta-, and delta-cells within intact islets of Langerhans. Tolbutamide elicits an increase in [Ca2+li in beta- and delta-cells, regardless of glucose concentrations. Remarkably, tolbutamide is without effect in alpha-cells. When diazoxide is applied, glucose-induced [Ca2+]i oscillations in beta- and delta-cells are abolished, whereas [Ca2+]i oscillations in alpha-cells remain unaltered. Furthermore, the existence of sulfonylurea receptors is demonstrated in beta-cells but not in alpha-cells by using binding of glybenclamide-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) combined with immunostaining for insulin and glucagon.
authors.affiliation: Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan, Alicante, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Quesada
authors.forename: A
authors.initials: A
authors.lastname: Nadal
authors.forename: B
authors.initials: B
authors.lastname: Soria
mesh_terms: D000818:Animals; D001896:Boron Compounds; D002118:Calcium / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D011955:Receptors, Drug / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014044:Tolbutamide / Q000494:pharmacology*
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D015221:Potassium Channels; D011955:Receptors, Drug; C067662:glibenclamide receptor; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium