The DOI matches its Crossref record.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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 the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Sorted by citations
The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
Cabrera, O., Berman, D. M., Kenyon, N. S., Ricordi, C., Berggren, P.-O., & Caicedo, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510790103 · Cited by 1,312
α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Gromada, J., Franklin, I., & Wollheim, C. B. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0007 · Cited by 596
Physiology of the pancreatic α-cell and glucagon secretion: role in glucose homeostasis and diabetes
Quesada, I., Tudurí, E., Ripoll, C., & Nadal, Á. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0290 · Cited by 447
Self-citationIslet β-cell secretion determines glucagon release from neighbouring α-cells
Ishihara, H., Maechler, P., Gjinovci, A., Herrera, P. L., & Wollheim, C. B. (2003) · Nature Cell Biology · doi:10.1038/ncb951 · Cited by 391
Nadal, Á., Ropero, A. B., Laribi, O., Maillet, M., Fuentes, E., & Soria, B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.21.11603 · Cited by 371
Self-citation
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
