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Cited by 132Pancreatic function and diabetesConnexins and lens biologyIon channel regulation and function

Critical Role of Gap Junction Coupled KATP Channel Activity for Regulated Insulin Secretion

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Rocheleau, Jonathan V, Remedi, Maria S, Granada, Butch, Head, W. Steven, Koster, Joseph C, Nichols, Colin G, Piston, David W·2006·PLoS Biology
DOI 10.1371/journal.pbio.0040026PMC PMC1334237
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Abstract

Pancreatic beta-cells secrete insulin in response to closure of ATP-sensitive K+ (KATP) channels, which causes membrane depolarization and a concomitant rise in intracellular Ca2+ (Cai). In intact islets, beta-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Cai oscillations after exposure to stimulatory glucose (>7 mM). To determine the significance of this coupling in regulating insulin secretion, we examined islets and beta-cells from transgenic mice that express zero functional KATP channels in approximately 70% of their beta-cells, but normal KATP channel density in the remainder. We found that KATP channel activity from approximately 30% of the beta-cells is sufficient to maintain strong glucose dependence of metabolism, Cai, membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of KATP channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell-cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus.

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  • Action potential firing in this subset of β-cells may trigger electrical activity in neighboring cells that lack Na+ channels by spread of depolarization via gap junctions.

    “Action potential firing in this subset of β-cells may trigger electrical activity in neighboring cells that lack Na+ channels by spread of depolarization via gap junctions (554).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [554]

    The Introduction (page not specified) describes synchronization of β-cell electrical activity through gap junctions. The Results/Discussion, including Figure 5 (page not specified), shows that coupling affects neighboring cells’ membrane potential and glucose-induced depolarization. The paper does not identify a firing subset defined by Na+ channels or say that action potentials from that subset trigger activity in neighbors lacking those channels. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In islets expressing non-functional KATP channels in 70% of β-cells, normal KATP channel activity in the remaining 30% of β-cells is sufficient to ensure nearly normal [Ca2+]i oscillations across the entire islet in response to glucose.

    “In islets expressing non-functional KATP channels in 70% of β-cells, normal KATP channel activity in the remaining 30% of β-cells is sufficient to ensure nearly normal [Ca2+]i oscillations across the entire islet in response to glucose (554).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [554]

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Authors
Rocheleau, J. V., Remedi, M. S., Granada, B., Head, W. S., Koster, J. C., Nichols, C. G., & Piston, D. W.
Affiliations
  • Vanderbilt University Medical Center (US)
  • Washington University in St. Louis (US)
Corresponding author
  • Nichols, Colin G
  • Piston, David W
ORCID
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2006-01-17
Volume
4
Issue
2
Pages
e26
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0040026
PMC
PMC1334237
OpenAlex
W2028641524
Cited by
132
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 8 · 2016: 5 · 2015: 4 · 2014: 15 · 2013: 8 · 2012: 6
FWCI
9.08
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (P20GM072048, GM072048)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK53434, R01DK053434, R01DK069445, DK-69445)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
electrical coupling, ATP-sensitive potassium channels, insulin secretion, pancreatic beta cells, calcium oscillations, membrane depolarization, glucose dependence, transgenic mice, neonatal diabetes
MeSH terms
Insulin Secretion, Animals, Calcium, Cations, Divalent, Cells, Cultured, Glucose, Insulin, Islets of Langerhans, Membrane Potentials, Models, Biological, Potassium Channels, Gap Junctions, Potassium Channels, Inwardly Rectifying, Tissue Culture Techniques

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