CoChat
Sign Up
Cited by 164Pancreatic function and diabetesIon channel regulation and functionIon Transport and Channel Regulation

A TP-Sensitive K+ Channel–Dependent Regulation of Glucagon Release and Electrical Activity by Glucose in Wild-Type and SUR1−/− Mouse α-Cells

Open access
Gromada, Jesper, Ma, Xiaosong, Høy, Marianne, Bokvist, Krister, Salehi, Albert, Berggren, Per-Olof, Rorsman, Patrik·2004·Diabetes
DOI 10.2337/diabetes.53.suppl_3.s181
Open this paper in CoChat — free accountOpen PDF

Abstract

Patch-clamp recordings and glucagon release measurements were combined to determine the role of plasma membrane ATP-sensitive K+ channels (KATP channels) in the control of glucagon secretion from mouse pancreatic α-cells. In wild-type mouse islets, glucose produced a concentration-dependent (half-maximal inhibitory concentration [IC50] = 2.5 mmol/l) reduction of glucagon release. Maximum inhibition (∼50%) was attained at glucose concentrations >5 mmol/l. The sulfonylureas tolbutamide (100 μmol/l) and glibenclamide (100 nmol/l) inhibited glucagon secretion to the same extent as a maximally inhibitory concentration of glucose. In mice lacking functional KATP channels (SUR1−/−), glucagon secretion in the absence of glucose was lower than that observed in wild-type islets and both glucose (0–20 mmol/l) and the sulfonylureas failed to inhibit glucagon secretion. Membrane potential recordings revealed that α-cells generate action potentials in the absence of glucose. Addition of glucose depolarized the α-cell by ∼7 mV and reduced spike height by 30% Application of tolbutamide likewise depolarized the α-cell (∼17 mV) and reduced action potential amplitude (43%). Whereas insulin secretion increased monotonically with increasing external K+ concentrations (threshold 25 mmol/l), glucagon secretion was paradoxically suppressed at intermediate concentrations (5.6–15 mmol/l), and stimulation was first detectable at >25 mmol/l K+. In α-cells isolated from SUR1−/− mice, both tolbutamide and glucose failed to produce membrane depolarization. These effects correlated with the presence of a small (0.13 nS) sulfonylurea-sensitive conductance in wild-type but not in SUR1−/− α-cells. Recordings of the free cytoplasmic Ca2+ concentration ([Ca2+]i) revealed that, whereas glucose lowered [Ca2+]i to the same extent as application of tolbutamide, the Na+ channel blocker tetrodotoxin, or the Ca2+ channel blocker Co2+ in wild-type α-cells, the sugar was far less effective on [Ca2+]i in SUR1−/− α-cells. We conclude that the KATP channel is involved in the control of glucagon secretion by regulating the membrane potential in the α-cell in a way reminiscent of that previously documented in insulin-releasing β-cells. However, because α-cells possess a different complement of voltage-gated ion channels involved in action potential generation than the β-cell, moderate membrane depolarization in α-cells is associated with reduced rather than increased electrical activity and secretion.

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 · 10.2337/diabetes.53.suppl_3.s181

Cites

45 of 45 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?

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

Cited by

Sorted by citations

Related

Authors
Gromada, J., Ma, X., Høy, M., Bokvist, K., Salehi, A., Berggren, P.-O., & Rorsman, P.
Affiliations
  • From the Lilly Research Laboratories, Hamburg, Germany
  • Lund University (SE)
  • University of Copenhagen (DK)
  • Karolinska Institutet (SE)
  • Churchill Hospital (GB)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2004-12-01
Volume
53
Issue
suppl_3
Pages
S181-S189
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.53.suppl_3.s181
OpenAlex
W2050636523
Cited by
164
References
45
Citations by year
2026: 4 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 12
FWCI
10.11
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
ATP-sensitive potassium channels, SUR1, glucagon secretion, alpha cells, glucose regulation, sulfonylureas, tolbutamide, glibenclamide, membrane potential, action potential, intracellular calcium, insulin secretion, islets, tetrodotoxin
MeSH terms
Adenosine Triphosphate, Animals, Glucagon, Glucose, Membrane Potentials, Mice, Inbred C57BL, Reference Values, Potassium Channels, Mice, Knockout, Mice

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