CoChat
Sign Up
Cited by 152Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

Chronic Palmitate Exposure Inhibits Insulin Secretion by Dissociation of Ca2+ Channels from Secretory Granules

Open access
Hoppa, Michael B., Collins, Stephan, Ramracheya, Reshma, Hodson, Leanne, Amisten, Stefan, Zhang, Quan, Johnson, Paul, Ashcroft, Frances M. +1 more·2009·Cell Metabolism
DOI 10.1016/j.cmet.2009.09.011PMC PMC2814048
Open this paper in CoChat — free accountOpen PDF

Abstract

Long-term (72 hr) exposure of pancreatic islets to palmitate inhibited glucose-induced insulin secretion by >50% with first- and second-phase secretion being equally suppressed. This inhibition correlated with the selective impairment of exocytosis evoked by brief (action potential-like) depolarizations, whereas that evoked by long ( approximately 250 ms) stimuli was unaffected. Under normal conditions, Ca(2+) influx elicited by brief membrane depolarizations increases [Ca(2+)](i) to high levels within discrete microdomains and triggers the exocytosis of closely associated insulin granules. We found that these domains of localized Ca(2+) entry become dispersed by long-term (72 hr), but not by acute (2 hr), exposure to palmitate. Importantly, the release competence of the granules was not affected by palmitate. Thus, the location rather than the magnitude of the Ca(2+) increase determines its capacity to evoke exocytosis. In both mouse and human islets, the palmitate-induced secretion defect was reversed when the beta cell action potential was pharmacologically prolonged.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2009.09.011

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • At 20 mM glucose, the time spent above -20 mV (the voltage where insulin granule exocytosis first becomes detectable) is ~30 ms.

    “Its width is somewhat variable but, at 20 mM glucose, the time spent above -20 mV (the voltage where insulin granule exocytosis first becomes detectable (222)) is ~30 ms (288).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [288]

    The Results section, under “Pharmacological Correction of the Inhibitory Action of Palmitate Exposure on Insulin Secretion” (page unavailable), reports action potentials averaging 31 ± 1 ms at 20 mM glucose, supporting the approximately 30 ms figure. It does not specify that this duration was measured as time above −20 mV; the citing sentence attaches a separate citation to the exocytosis-threshold explanation. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Similar values for granule density have been obtained by live-cell imaging using fluorescently tagged granules: 0.8 granule/μm2 in mouse β-cells and 0.7 granules/μm2 in human β-cells.

    “Similar values for granule density have been obtained by live-cell imaging using fluorescently tagged granules: 0.8 granule/μm2 in mouse β-cells (288)and 0.7 granules/μm2 in human β-cells (447).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [288]

    In Results, under “Inhibition of Rapid Exocytosis in Palmitate-Treated Cells” (page unavailable), the paper reports granule density from fluorescent imaging in β-cells, but gives approximately 0.7 granules/μm², not the cited 0.8 granules/μm². The human-cell value has a separate citation in the citing sentence and is not attributed to this paper. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In the latter studies, most near-membrane granules were immobile, confirming they were functionally as well as morphologically docked.

    “In the latter studies, most of these near-membrane granules were immobile, thus confirming they were functionally as well as morphologically docked (49, 288).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [288]

    The Results section, ‘Inhibition of Rapid Exocytosis in Palmitate-Treated Cells’ (page unavailable), calls the near-membrane granules docked and reports that 20%–25% were released during stimulation. The paper does not report that most near-membrane granules were immobile or establish immobility as confirmation of functional docking. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • There is general agreement that many docked granules are released in response to membrane depolarization produced by sulfonylureas or high [K+]o.

    “There is general agreement that many docked granules are released in response to membrane depolarization produced by sulfonylureas or high [K+]o (288, 446, 487, 617).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [288]

    The Results section (“Inhibition of Rapid Exocytosis in Palmitate-Treated Cells”; page not provided) reports that 20%–25% of docked granules were released during a train of prolonged electrical depolarizations. The Discussion says tolbutamide triggers brief action potentials, but our copy does not show that sulfonylureas or high extracellular K+ produced the reported docked-granule release. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Frayn K.N. Metabolic Regulation: A Human Perspective 2003 Blackwell Science Oxford

Cited by

Sorted by citations

Authors
Hoppa, M. B., Collins, S., Ramracheya, R., Hodson, L., Amisten, S., Zhang, Q., Johnson, P., Ashcroft, F. M., & Rorsman, P.
Affiliations
  • Churchill Hospital (GB)
  • John Radcliffe Hospital (GB)
  • University of Oxford (GB)
Corresponding author
Rorsman, Patrik
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2009-12
Volume
10
Issue
6
Pages
455-465
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2009.09.011
PMC
PMC2814048
OpenAlex
W2069730743
Cited by
152
References
43
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 7 · 2015: 13 · 2014: 13 · 2013: 11 · 2012: 8
FWCI
11.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Wellcome Trust (084655)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
palmitate, insulin secretion, pancreatic beta cells, calcium channels, secretory granules, exocytosis, calcium microdomains, calcium influx, glucose-stimulated insulin secretion, action potential duration, long-chain fatty acids, islets
MeSH terms
Insulin Secretion, Animals, Calcium, Electrophysiology, Exocytosis, Humans, Insulin, Islets of Langerhans, Membrane Potentials, Palmitates, Calcium Channels, Secretory Vesicles, Insulin-Secreting Cells, 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