Different effects of tolbutamide and diazoxide in alpha, beta-, and delta-cells within intact islets of Langerhans.
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.
Quesada
I
I
Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan, Alicante, Spain.
Nadal
A
A
Soria
B
B
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*
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