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Cited by 272Pancreatic function and diabetesIon channel regulation and functionDiabetes Treatment and Management

KATP channels and islet hormone secretion: new insights and controversies

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Ashcroft, Frances M., Rorsman, Patrik·2013·Nature Reviews Endocrinology
DOI 10.1038/nrendo.2013.166PMC PMC5890885
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Abstract

ATP-sensitive potassium channels (K(ATP) channels) link cell metabolism to electrical activity by controlling the cell membrane potential. They participate in many physiological processes but have a particularly important role in systemic glucose homeostasis by regulating hormone secretion from pancreatic islet cells. Glucose-induced closure of K(ATP) channels is crucial for insulin secretion. Emerging data suggest that K(ATP) channels also play a key part in glucagon secretion, although precisely how they do so remains controversial. This Review highlights the role of K(ATP) channels in insulin and glucagon secretion. We discuss how K(ATP) channels might contribute not only to the initiation of insulin release but also to the graded stimulation of insulin secretion that occurs with increasing glucose concentrations. The various hypotheses concerning the role of K(ATP) channels in glucagon release are also reviewed. Furthermore, we illustrate how mutations in K(ATP) channel genes can cause hyposecretion or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, and how defective metabolic regulation of the channel may underlie the hypoinsulinaemia and the hyperglucagonaemia that characterize type 2 diabetes mellitus. Finally, we outline how sulphonylureas, which inhibit K(ATP) channels, stimulate insulin secretion in patients with neonatal diabetes mellitus or type 2 diabetes mellitus, and suggest their potential use to target the glucagon secretory defects found in diabetes mellitus.

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  • Gain-of-function mutations in either Kir6.2 or SUR1 result in neonatal diabetes, which usually presents within the first six months of life and is associated with a low birth weight.

    “Gain-of-function mutations in either Kir6.2 or SUR1 result in neonatal diabetes (ND), which usually presents within the first six months of life and is associated with a low birth weight (25, 29, 32, 43, 215, 255).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [32]

    The “Neonatal diabetes mellitus” section says gain-of-function mutations in Kir6.2 or SUR1 cause neonatal diabetes and that reduced insulin secretion leads to low birth weight. It says the disease usually presents within the first 6–9 months of life, not specifically within the first six months. No page number is provided in our copy. (LLM, conf=0.88)

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Authors
Ashcroft, F. M., & Rorsman, P.
Affiliations
  • University of Oxford (GB)
  • Churchill Hospital (GB)
Corresponding author
Ashcroft, Frances M.
ORCID
Venue
Nature Reviews Endocrinology
Publisher
Springer Science and Business Media LLC
Published
2013-09-17
Volume
9
Issue
11
Pages
660-669
ISSN
  • 1759-5029 (ISSN-L)
  • 1759-5037
DOI
10.1038/nrendo.2013.166
PMC
PMC5890885
OpenAlex
W2062880748
Cited by
272
References
17
Citations by year
2026: 13 · 2025: 18 · 2024: 16 · 2023: 18 · 2022: 25 · 2021: 27 · 2020: 20 · 2019: 24 · 2018: 28 · 2017: 27 · 2016: 18 · 2015: 23 · 2014: 15
FWCI
3.30
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Wellcome Trust (084655, 095531/Z/11/Z, 095531)
  • Royal Society
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Surgery › 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
ATP-sensitive potassium channels, insulin secretion, glucagon secretion, glucose homeostasis, neonatal diabetes, congenital hyperinsulinism, type 2 diabetes, sulfonylureas, KATP channel mutations, hyperglucagonaemia, hypoinsulinaemia
MeSH terms
Insulin Secretion, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin, Islets of Langerhans, Potassium Channels, Inwardly Rectifying

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