Evidence map›Paper›PMID 10318919›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1999

The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein.

S Barg, E Renström, P O Berggren, A Bertorello, K Bokvist, M Braun, L Eliasson, W E Holmes, M Köhler, P Rorsman and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 69 citations in OpenAlex.

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  12. Fluid shear-induced ATP secretion mediates prostaglandin release in MC3T3-E1 osteoblasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2005
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

S BargDepartment of Physiological Sciences, Lund University, Sölvegatan 19, S-223 62 Lund, Sweden.
E Renström
P O Berggren
A Bertorello
K Bokvist
M Braun
L Eliasson
W E Holmes
M Köhler
P Rorsman
F Thévenod
Novo Nordisk (Denmark) · DKKarolinska Institutet · SESaarland University · DELund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular application of the sulfonylurea tolbutamide during whole-cell patch-clamp recordings stimulated exocytosis >5-fold when applied at a cytoplasmic Ca2+ concentration of 0.17 microM. This effect was not detectable in the complete absence of cytoplasmic Ca2+ and when exocytosis was elicited by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The stimulatory action could be antagonized by the sulfonamide diazoxide, by the Cl--channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), by intracellular application of the antibody JSB1 [originally raised against a 170-kDa multidrug resistance (mdr) protein], and by tamoxifen (an inhibitor of the mdr- and volume-regulated Cl- channels). Immunocytochemistry and Western blot analyses revealed that JSB1 recognizes a 65-kDa protein in the secretory granules. This protein exhibited no detectable binding of sulfonylureas and is distinct from the 140-kDa sulfonylurea high-affinity sulfonylurea receptors also present in the granules. We conclude that (i) tolbutamide stimulates Ca2+-dependent exocytosis secondary to its binding to a 140-kDa high-affinity sulfonylurea receptor in the secretory granules; and (ii) a granular 65-kDa mdr-like protein mediates the action. The processes thus initiated culminate in the activation of a granular Cl- conductance. We speculate that the activation of granular Cl- fluxes promotes exocytosis (possibly by providing the energy required for membrane fusion) by inducing water uptake and an increased intragranular hydrostatic pressure.

Indexed as

ATP-Binding Cassette TransportersPotassium Channels, Inwardly Rectifying4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsAntibodies, MonoclonalATP Binding Cassette Transporter, Subfamily B, Member 1CalciumCells, CulturedCytoplasmic GranulesDiabetes Mellitus, Type 2Drug Resistance, MultipleExocytosisGlyburideIslets of LangerhansMiceMice, Inbred Strains4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAntibodies, MonoclonalATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1CalciumGlyburidePotassium ChannelsPotassium Channels, Inwardly RectifyingReceptors, DrugSulfonylurea ReceptorsTolbutamide

Identifiers

PMID10318919
PMCPMC21895
OpenAlexW2084535455

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.