Evidence map›Paper›PMID 35196393›Full record

ReviewDiabetes2022

ATP-Sensitive Potassium Channels in Hyperinsulinism and Type 2 Diabetes: Inconvenient Paradox or New Paradigm?

Colin G Nichols, Nathaniel W York, Maria S Remedi

Open access · bronzeAbstract readReview
In one paragraph

Review in Diabetes, 2022. 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
5.4field-weighted citation impact, top 3% 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, 27 citations in OpenAlex.

  1. Article
  2. Is high insulin protective or detrimental? Mathematical modeling reveals the base of the iceberg.American journal of physiology. Endocrinology and metabolism · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Bayliss-Starling Prize Lecture: KThe Journal of physiology · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. CaFrontiers in endocrinology · 2024
    Review
  15. Clinical management of diazoxide-unresponsive congenital hyperinsulinism: A single-center experience.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2024
    Article
  16. Article
  17. Article
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

3 authors at 1 institution in 1 country.

Colin G NicholsCenter for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO.ORCID 0000-0002-4929-2134
Nathaniel W YorkCenter for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO.
Maria S RemediCenter for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO.ORCID 0000-0003-2048-472X
Washington University in St. Louis · US

Funding

Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Jonathan R Brestoff · 1999 to 2026
$30.2M
Role of vascular KATP channels in Alzheimer’s neurodegeneration and dementiaR35HL140024 · NHLBI · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 2018 to 2023
$5.9M
Beta-Cell Exhaustion and Glucotoxicity in DiabetesR01DK123163 · NIDDK · WASHINGTON UNIVERSITY · PI Maria Sara Remedi · 2020 to 2026
$2.8M
NHLBI NIH HHS R35 HL140024NIDDK NIH HHS P30 DK056341NIDDK NIH HHS R01 DK123163
6 · The paper itself

Abstract

Secretion of insulin from pancreatic β-cells is complex, but physiological glucose-dependent secretion is dominated by electrical activity, in turn controlled by ATP-sensitive potassium (KATP) channel activity. Accordingly, loss-of-function mutations of the KATP channel Kir6.2 (KCNJ11) or SUR1 (ABCC8) subunit increase electrical excitability and secretion, resulting in congenital hyperinsulinism (CHI), whereas gain-of-function mutations cause underexcitability and undersecretion, resulting in neonatal diabetes mellitus (NDM). Thus, diazoxide, which activates KATP channels, and sulfonylureas, which inhibit KATP channels, have dramatically improved therapies for CHI and NDM, respectively. However, key findings do not fit within this simple paradigm: mice with complete absence of β-cell KATP activity are not hyperinsulinemic; instead, they are paradoxically glucose intolerant and prone to diabetes, as are older human CHI patients. Critically, despite these advances, there has been little insight into any role of KATP channel activity changes in the development of type 2 diabetes (T2D). Intriguingly, the CHI progression from hypersecretion to undersecretion actually mirrors the classical response to insulin resistance in the progression of T2D. In seeking to explain the progression of CHI, multiple lines of evidence lead us to propose that underlying mechanisms are also similar and that development of T2D may involve loss of KATP activity.

Indexed as

AnimalsBlood GlucoseCalciumCongenital HyperinsulinismDiabetes Mellitus, Type 2HumansInsulin ResistanceInsulin SecretionKATP ChannelsKcnj11 ChannelMiceMice, KnockoutMutationPotassium Channels, Inwardly RectifyingSulfonylurea ReceptorsABCC8 protein, humanAbcc8 protein, mouseBlood GlucoseCalciumKATP ChannelsKcnj11 ChannelPotassium Channels, Inwardly RectifyingSulfonylurea Receptors

Identifiers

PMID35196393
PMCPMC8893938
OpenAlexW4213359169

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.