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.
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Rat alpha cells have much higher KATP channel density than mouse alpha cells.
“Similar evidence has been obtained with rat alpha cells, which have much higher K ATP channel density [43] than mouse alpha cells [13,44].”
From Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells (2007) · cites this paper as [44]
In isolated mouse alpha cells with low KATP channel density, the inhibitory effect of glucose dominated, although closure of the KATP channels themselves was modestly stimulatory.
“In isolated mouse alpha cells with low K ATP channel density [13,44] the inhibitory effect of glucose dominated, although closure of the K ATP channels themselves was modestly stimulatory.”
From Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells (2007) · cites this paper as [44]
Mouse alpha-cells show little KATP channel expression, corresponding to 2% of that in mouse beta-cells.
“mouse ␣-cells show little K ATP channel expression (25,26), corresponding to 2% of that in mouse -cells (27).”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [25]
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“However, cells included in this study showed [Ca2C]i responses to tolbutamide, tolbutamide in combination with glucose, and arginine that were all typical for b-cells (Berts et al. 1996, Quesada et al. 1999).”
BackgroundHyperinsulinemia predicts survival in a hyperglycemic mouse model of critical illness*
Woodske, M. E., Yokoe, T., Zou, B., Romano, L. C., Rosa, T. C., Garcı́a-Ocaña, A., Alonso, L. C., O'Donnell, C. P., & McVerry, B. J. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181a9338a · Cited by 8 · see citing works
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Ingeniería celular y diabetes mellitus
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Electrophysiology of Islet Cells
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Electrophysiology of Islet Cells
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- Authors
- Quesada, I., Nadal, A., & Soria, B.
- Affiliations
- Universitat de Miguel Hernández d'Elx (ES)
- Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan, Alicante, Spain.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-12-01
- Volume
- 48
- Issue
- 12
- Pages
- 2390-2397
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2106272975
- Cited by
- 99
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 3
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- tolbutamide, diazoxide, pancreatic islets, alpha cells, pancreatic beta cells, delta cells, intracellular calcium, calcium oscillations, sulfonylurea receptor, sulfonylureas, sulfonamides, ATP-sensitive potassium channels, insulin secretion, glucagon, type 2 diabetes, glibenclamide
- MeSH terms
- Animals, Boron Compounds, Calcium, Diazoxide, Fluorescent Dyes, Glyburide, Glucose, Islets of Langerhans, Kinetics, Mice, Inbred Strains, Receptors, Drug, Tolbutamide, Potassium Channels, Signal Transduction, Mice, In Vitro Techniques
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