ArticleDiabetologia2015
LKB1 couples glucose metabolism to insulin secretion in mice.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- Liver kinase B1 (LKB1) regulates the epigenetic landscape of mouse pancreatic beta cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Review
- Of Mice and Men and Plethysmography Systems: Does LKB1 Determine the Set Point of Carotid Body Chemosensitivity and the Hypoxic Ventilatory Response?Advances in experimental medicine and biology · 2023Article
- ROCK1 regulates insulin secretion from β-cells.Molecular metabolism · 2022Article
- LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response.Communications biology · 2022Article
- Islet Biology During COVID-19: Progress and Perspectives.Canadian journal of diabetes · 2022Review
- Large-Scale Functional Genomics Screen to Identify Modulators of Human β-Cell Insulin Secretion.Biomedicines · 2022Article
- Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice.International journal of molecular medicine · 2020Article
- Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass.Diabetologia · 2019Article
- Article
- Transcription factor-7-like 2 (The Journal of biological chemistry · 2018Article
- A Novel Phenylchromane Derivative Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating AMPK.Pharmaceutical research · 2017Article
- Identification of the signals for glucose-induced insulin secretion in INS1 (832/13) β-cells using metformin-induced metabolic deceleration as a model.The Journal of biological chemistry · 2017Article
- Sirolimus induces depletion of intracellular calcium stores and mitochondrial dysfunction in pancreatic beta cells.Scientific reports · 2017Article
- High-throughput Functional Genomics Identifies Regulators of Primary Human Beta Cell Proliferation.The Journal of biological chemistry · 2016Article
- Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells.Diabetologia · 2016Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
aims/hypothesisPrecise regulation of insulin secretion by the pancreatic beta cell is essential for the maintenance of glucose homeostasis. Insulin secretory activity is initiated by the stepwise breakdown of ambient glucose to increase cellular ATP via glycolysis and mitochondrial respiration. Knockout of Lkb1, the gene encoding liver kinase B1 (LKB1) from the beta cell in mice enhances insulin secretory activity by an undefined mechanism. Here, we sought to determine the molecular basis for how deletion of Lkb1 promotes insulin secretion.
methodsTo explore the role of LKB1 on individual steps in the insulin secretion pathway, we used mitochondrial functional analyses, electrophysiology and metabolic tracing coupled with by gas chromatography and mass spectrometry.
resultsBeta cells lacking LKB1 surprisingly display impaired mitochondrial metabolism and lower ATP levels following glucose stimulation, yet compensate for this by upregulating both uptake and synthesis of glutamine, leading to increased production of citrate. Furthermore, under low glucose conditions, Lkb1(-/-) beta cells fail to inhibit acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in lipid synthesis, and consequently accumulate NEFA and display increased membrane excitability. CONCLUSIONS/
interpretationTaken together, our data show that LKB1 plays a critical role in coupling glucose metabolism to insulin secretion, and factors in addition to ATP act as coupling intermediates between feeding cues and secretion. Our data suggest that beta cells lacking LKB1 could be used as a system to identify additional molecular events that connect metabolism to cellular excitation in the insulin secretion pathway.
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Registered trials
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.